Chitin,distinguished by its nitrogen-rich acetamido and amino groups,imparts a distinctive cationic nature,enabling chitin to have indispensable features in various applications.Despite its significant promise in the ...Chitin,distinguished by its nitrogen-rich acetamido and amino groups,imparts a distinctive cationic nature,enabling chitin to have indispensable features in various applications.Despite its significant promise in the textile industry,particularly for sustainable and functional fabric applications,the practical utilization of chitin fibers remains constrained by insufficient mechanical strength.The degree of deacetylation(DD),a key molecular-level structural determinant,has not been adequately addressed in previous studies despite its critical role in influencing chitin properties across multiple scales.In this study,a deacetylation-mediated design strategy was used to achieve enhanced mechanical performance coupled with multifunctional efficacy using an aqueous KOH/urea solution dissolution system.We prepared a series of deacetylated chitins with different DD values and systematically studied the effect of deacetylation on the multiple-scale structure of regenerated fibers,such as intermolecular interactions and chain orientation at the molecular level,and the aggregation behavior of chitin nanofibers within the gel-state and dried fibers at the micro/nano scale.To achieve an enhanced mechanical performance coupled with multifunctional efficacy by relying on an aqueous KOH/urea solution dissolution system.Moreover,deacetylation enhances intermolecular interactions,resulting in densified internal structures and improved fiber orientation.Concomitantly,it augmented the antimicrobial functionality of the fibers.This deacetylation-mediated design strategy provides a deeper understanding of the structure and properties of regenerated chitin and advances the utility of chitin in strong and sustainable fibers.展开更多
Trans-(-)-ε-viniferin(ε-viniferin)has antioxidative and anti-inflammatory effects.It also has neuroprotective effects in Huntington's disease by activating the SIRT3/LKB1/AMPK signaling pathway;however,it remain...Trans-(-)-ε-viniferin(ε-viniferin)has antioxidative and anti-inflammatory effects.It also has neuroprotective effects in Huntington's disease by activating the SIRT3/LKB1/AMPK signaling pathway;however,it remains unknown whetherε-viniferin also has a neuroprotective role in Parkinson's disease.A Parkinson's disease cell model was induced by exposing SH-SY5 Y cells to 3.0μM rotenone for 24 hours,and cells were then treated with 1.0μMε-viniferin for 24 hours.Treatment withε-viniferin upregulated SIRT3 expression,which promoted FOXO3 deacetylation and nuclear localization.ε-Viniferin also increased ATP production and decreased reactive oxygen species production.Furthermore,ε-viniferin treatment alleviated rotenone-induced mitochondrial depolarization and reduced cell apoptosis,and restored the expression of mitochondrial homeostasis-related proteins.However,when cells were transfected with SIRT3 or FOXO3 shRNA prior to rotenone andε-viniferin treatment,these changes were reversed.The results from the present study indicate thatε-viniferin enhances SIRT3-mediated FOXO3 deacetylation,reduces oxidative stress,and maintains mitochondrial homeostasis,thus inhibiting rotenone-induced cell apoptosis.ε-Viniferin may therefore be a promising treatment strategy for Parkinson's disease.展开更多
AIM: To explore the effects of IκBα SUMOylation and NF-κB p65 deacetylation on NF-κB p65 activity induced by high glucose in cultured human lens epithelial cells(HLECs).METHODS: HLECs(SRA01/04) were cultured with ...AIM: To explore the effects of IκBα SUMOylation and NF-κB p65 deacetylation on NF-κB p65 activity induced by high glucose in cultured human lens epithelial cells(HLECs).METHODS: HLECs(SRA01/04) were cultured with 5.5, 25, and 50 mmol/L glucose media for 24 h, and with 50 mmol/L glucose media for 0, 12, and 24 h respectively. SUMO1 and SIRT1 expressions were detected by reverse transcriptionpolymerase chain reaction(RT-PCR) and Western blot(WB). IκBα and NF-κB p65 expressions were detected by WB. With NAC, DTT, MG132 or Resveratrol(RSV) treatment, SUMO1 and SIRT1 expressions were detected by WB. Protein expression localizations were examined by immunofluorescence and co-immunofluorescence. The effects of SUMO1 or SIRT1 overexpression, as well as MG132 and RSV, on the nuclear expression and activity of IκBα and NF-κB p65 were analyzed by immunoblot and dual luciferase reporter gene assay.RESULTS: SUMO1 and SIRT1 expressions were influenced by high glucose in mRNA and protein levels, which could be blocked by NAC or DTT. SUMO1 was down-regulated by using MG132, and SIRT1 was up-regulated under RSV treatment. IκBα nuclear expression was attenuated and NF-κB p65 was opposite under high glucose, while IκBα and NF-κB p65 location was transferred to the nucleus. SUMO1 or SIRT1 overexpression and MG132 or RSV treatment affected the nuclear expression and activity of IκBα and NF-κB p65 under high glucose condition.CONCLUSION: IκBα SUMOylation and NF-κB p65 deacetylation affect NF-κB p65 activity in cultured HLECs under high glucose, and presumably play a significant role in controlling diabetic cataract.展开更多
Chitin and chitosan films were prepared by solution casting method. Chitosan specimens used in this study were deacetylated by 50.4%, 69.2%, 85.5% and 96.3%. Their water content, protein adhesion ability, cytocompatib...Chitin and chitosan films were prepared by solution casting method. Chitosan specimens used in this study were deacetylated by 50.4%, 69.2%, 85.5% and 96.3%. Their water content, protein adhesion ability, cytocompatibility, cell adhesion ability, in vitro and vivo degradability and biocompatibility were evaluated. Results indicated that with the degree of deacetylation （DD） between 50% and 70%, the chitosan showed higher water content. The higher the DD, the stronger protein adhesion ability the chitosan had. All the films have good cytocompatibility and the films with higher DD have better cell adhesion ability. Chitin films degraded more rapidly than others, which disappeared in 2 to 4 weeks after they were implanted in subcutaneous tissue and musculature. Their inflammatory reaction became weaker as the films degraded. As the DD got higher, the films degraded slower. The films of DD 85.5% and DD 90.3% even didn＇t disappeared in 12 weeks after they were implanted. Their inflammatory reaction was mild at the beginning of degradation, and became severe in 4 to 8 weeks, then weaken at last. This basic result can be very helpful for tissue engineering.展开更多
The acetyl ester plays an important role for protection of the hydroxyl groups in carbohydrates synthesis.In the present study,we described an efficient deprotection of acetyl group of pentacyclic triterpenoid by usin...The acetyl ester plays an important role for protection of the hydroxyl groups in carbohydrates synthesis.In the present study,we described an efficient deprotection of acetyl group of pentacyclic triterpenoid by using methanolic ammonia in THF solution.Good selectivity for cleaving gal-C2-OAc group of 3β-hydroxy-olean-12-en-28-oic acid 28-N-2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside(3) was achieved in the presence of methanolic ammonia within 4 h at low temperature(-60℃) in a yield of 56%.The reaction disclosed here provides a new method for the synthesis of C2 selective modified carbohydrates,which is more useful than conventional synthesis procedure that usually requires many steps including temporary regioselective protection and deprotection.When the reaction temperature was increased from -60℃ to room temperature,the cleavage of the other three acetyl groups of galactose in an order of C4-OAc>C3-OAc>C6-OAc was observed.Based on this study,a plausible route for the deacetylation reaction has been proposed.展开更多
Wheat root systems undergo dynamic and adaptive changes to mitigate adverse effects through sophisticated regulatory mechanisms under drought stress.Elucidating and utilizing these mechanisms is highly important for b...Wheat root systems undergo dynamic and adaptive changes to mitigate adverse effects through sophisticated regulatory mechanisms under drought stress.Elucidating and utilizing these mechanisms is highly important for breeding drought-resistant wheat varieties.Here,we identify histone deacetylase TaHDA8 as a critical component that negatively regulates wheat root elongation and drought tolerance.Under drought stress,TaHDA8 could be finely tuned to alleviate its inhibition of root elongation,thereby improving wheat adaptation to water deficit.Interestingly,reduction in TaHDA8 protein levels de-represses the DNA-binding ability of TaAREB3,a positive regulator of root elongation and drought tolerance,which depends on the retention of acetylation at K248 and K281 residues.The restored DNA binding of TaAREB3 to the promoter of TaKOR1 upregulates its expression,thereby promoting root elongation by enhancing cell proliferation in the root meristem.Further studies revealed that natural variations in the TaKOR1 promoter determine the differences in TaAREB3 binding,and wheat germplasm with TaHDA8–TaAREB3–TaKOR1 regulatory module has been widely selected.Collectively,this study reveals how a lysine deacetylase regulates drought-responsive root development via non-histone deacetylation,providing genetic resources for improving root architecture and breeding drought-resilient wheat varieties.展开更多
The shift from skotomorphogenesis to photomorphogenesis,a developmental transition in seed plants,in-volves dramatic proteomic changes.Lysine acetylation(Lys-Ac)is an evolutionarily conserved and recog-nized post-tran...The shift from skotomorphogenesis to photomorphogenesis,a developmental transition in seed plants,in-volves dramatic proteomic changes.Lysine acetylation(Lys-Ac)is an evolutionarily conserved and recog-nized post-translational modification that plays a crucial role in plant development.However,its role in seedling deetiolation remains unclear.In this study,we conducted a comparative lysine acetylomic anal-ysis of etiolated Arabidopsis seedlings before and after red(R)light irradiation,uncovering that exposure to R light mainly led to protein lysine deacetylation during seedling deetiolation.Phytochrome A(phyA),a unique far-red(FR)light photoreceptor,was deacetylated at lysine 65(K65)when etiolated seedlings were moved to light.This residue is a critical ubiquitination site that regulates phyA stability.Moreover,K65 deacetylation facilitates phyA ubiquitination and 26s proteasome-mediated degradation,and is required for the function of phyA in FR light signaling and seedling photomorphogenesis.Furthermore,we identified a plant-specific lysine deacetylase HDT2 that interacts with and deacetylates phyA in the nu-cleus to promote its ubiquitination and degradation during seedling deetiolation.Genetic analysis revealed that HDT2 is critical for phyA-mediated photomorphogenic growth.Taken together,these findings reveal that lysine deacetylation of phyA by HDT2 plays a crucial role in modulating phyA turnover in response to light,suggesting that Lys-Ac might be central to the reprogramming of plants for photomorphogenic growth.展开更多
The infiltration of glioblastoma multiforme(GBM)is predominantly characterized by diffuse spread,contributing significantly to therapy resistance and recurrence of GBM.In this study,we reveal that microtubule deacetyl...The infiltration of glioblastoma multiforme(GBM)is predominantly characterized by diffuse spread,contributing significantly to therapy resistance and recurrence of GBM.In this study,we reveal that microtubule deacetylation,mediated through the downregulation of fibronectin type III and SPRY domain-containing 1(FSD1),plays a pivotal role in promoting GBM diffuse infiltration.FSD1 directly interacts with histone deacetylase 6(HDAC6)at its second catalytic domain,thereby impeding its deacetylase activity onα-tubulin and preventing microtubule deacetylation and depolymerization.This inhibitory interaction is disrupted upon phosphorylation of FSD1 at its Ser317 and Ser324 residues by activated CDK5,leading to FSD1 dissociation from microtubules and facilitating HDAC6-mediatedα-tubulin deacetylation.Furthermore,increased expression of FSD1 or interference with FSD1 phosphorylation reduces microtubule deacetylation,suppresses invasion of GBM stem cells,and ultimately mitigates tumor infiltration in orthotopic GBM xenografts.Importantly,GBM tissues exhibit diminished levels of FSD1 expression,correlating with microtubule deacetylation and unfavorable clinical outcomes in GBM patients.These findings elucidate the mechanistic involvement of microtubule deacetylation in driving GBM cell invasion and offer potential avenues for managing GBM infiltration.展开更多
Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid pla- que pathogenesis in Alzheimer＇s disease （AD）. Recent evidence suggests that lysosomal dysfunction leads to i...Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid pla- que pathogenesis in Alzheimer＇s disease （AD）. Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB （TFEB）, an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ （fAβ） degra- dation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APPIPS1 transgenic mice. Our findings reveal that deacetylaUon of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.展开更多
The p53 tumor suppressor is a sequence-specific transcription factor that undergoes an abundance of post-translational modifications for its regulation and activation.Acetylation of p53 is an important reversible enzy...The p53 tumor suppressor is a sequence-specific transcription factor that undergoes an abundance of post-translational modifications for its regulation and activation.Acetylation of p53 is an important reversible enzymatic process that occurs in response to DNA damage and genotoxic stress and is indispensible for p53 transcriptional activity.p53 was the first non-histone protein shown to be acetylated by histone acetyl transferases,and a number of more recent in vivo models have underscored the importance of this type of modification for p53 activity.Here,we review the current knowledge and recent findings of p53 acetylation and deacetylation and discuss the implications of these processes for the p53 pathway.展开更多
In eukaryotes,histone acetylation is a major modification on histone N-terminal tails that is tightly connected to transcriptional activation.HDA6 is a histone deacetylase involved in the transcriptional regulation of...In eukaryotes,histone acetylation is a major modification on histone N-terminal tails that is tightly connected to transcriptional activation.HDA6 is a histone deacetylase involved in the transcriptional regulation of genes and transposable elements(TEs)in Arabidopsis thaliana.HDA6 has been shown to participate in several complexes in plants,including a conserved SIN3 complex.Here,we uncover a novel protein complex containing HDA6,several Harbinger transposon-derived proteins(HHP1,SANT1,SANT2,SANT3,and SANT4),and MBD domain-containing proteins(MBD1,MBD2,and MBD4).We show that mutations of all four SANT genes in the sant-null mutant cause increased expression of the flowering repressors FLC,MAF4,and MAF5,resulting in a late flowering phenotype.Transcriptome deep sequencing reveals that while the SANT proteins and HDA6 regulate the expression of largely overlapping sets of genes,TE silencing is unaffected in sant-null mutants.Our global histone H3 acetylation profiling shows that SANT proteins and HDA6 modulate gene expression through deacetylation.Collectively,our findings suggest that Harbinger transposon-derived SANT domain-containing proteins are required for histone deacetylation and flowering time control in plants.展开更多
TANK-binding kinase 1(TBK1),a core kinase of antiviral pathways,activates the production of interferons(IFNs).It has been reported that deacetylation activates TBK1;however,the precise mechanism still remains to be un...TANK-binding kinase 1(TBK1),a core kinase of antiviral pathways,activates the production of interferons(IFNs).It has been reported that deacetylation activates TBK1;however,the precise mechanism still remains to be uncovered.We show here that during the early stage of viral infection,the acetylation of TBK1 was increased,and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1.HDAC3 directly deacety-lated TBK1 at Lys241 and Lys692,which resulted in the activation of TBK1.Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively.Using knockout cell lines and transgenic mice,we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs.Furthermore,activated TBK1 phosphorylated HDAC3,which promoted the deacetylation activity of HDAC3 and formed a feedback loop.In this study,we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-trans-lational modulations involved in the interaction between TBK1 and HDAC3.展开更多
This paper presents experimental results on the effect of alkalis such as NaOH, KOH and Ca（OH）2 on deacetylation of a konjac glucomannan （KGM） powder under mechano-chemical （MC） treatment, The results show that ...This paper presents experimental results on the effect of alkalis such as NaOH, KOH and Ca（OH）2 on deacetylation of a konjac glucomannan （KGM） powder under mechano-chemical （MC） treatment, The results show that the alkalinity of modifiers is a dominant factor for deacetylation of KGM, In addition, characteristics, such as swelling property, viscous stability and thermal behavior of the deacetylated KGM are analyzed展开更多
In eukaryotes, nucleosome is the basic unit of chromatin. Nucleosome is composed of an octamer of histone proteins (two molecules each of histones H 2A , H 2B , H 3 and H 4) and DNA strand wound around the octamer. So...In eukaryotes, nucleosome is the basic unit of chromatin. Nucleosome is composed of an octamer of histone proteins (two molecules each of histones H 2A , H 2B , H 3 and H 4) and DNA strand wound around the octamer. Some data show that core histone octamer can affect gene transcription both \%in vitro\% and \%in vivo.\% Recent results indicate that histone acetylation/deacetylation is a key step to regulate activity of genes. This article summarizes some coactivators, such as GCN5p, P300/CBP and TAF Ⅱ 250, which are recently found to have histone acetyltransferase activity. The relationship between these coactivators and gene activation is also described. Besides, this article concerns some corepressors which have histone deacetylase activity, such as Rpd3p, HDAC2. These corepressors combine with other protein complex and then repress transcription. Finally, some problems to be solved and the future direction in this active field are discussed.展开更多
Production of chitosan and its derivatives by traditional methods involves the excessive use of a reaction solution comprisedof sodium hydroxide and hydrochloric acid. Waste water resulting from this process has lim让...Production of chitosan and its derivatives by traditional methods involves the excessive use of a reaction solution comprisedof sodium hydroxide and hydrochloric acid. Waste water resulting from this process has lim让ed the application of chitosanas a fertilizer as the process causes serious environmental pollution. Specifically, the resulting waste water contains highlevels of dissolved nitrogen and minerals from shrimp shells. In this study, an eco-friendly method was established to produce chitooligosaccharides (COS) with different degrees of deacetylation (DDAs) from shrimp shell waste. At a solid-tosolventratio of 1:6, the degree of demineralization was above 90% with the treatment of 30 g-L_1 H3PO4, and the degree ofdeproteinization was above 80% when treated with 30 g-L_1 KOH at 70 °C. Chitosans with different DDAs were obtainedby microwave-assisted KOH metathesis and the COS with Mw approximately 1500 Da were then prepared by oxidativedegradation. In summary, 33.73 kg H3PO4,12.77 kg, and 241.31 kg KOH were supplied during the processes of demineralization,deproteinization, and deacetylation of 100 kg shrimp shell waste, respectively. The process water was totally recycled,demonstrating that the shrimp shell could be wholly transformed into fertilize The entire process created a product withthe fractions of N:P2O5:K2O:COS = 7.94:24.44:10.72:1 &27. The test on the germination promotion of wheat seeds revealedthat the COS with 72」2% DDA significantly promoted germination. This work demonstrated the use of an eco-friendlypreparation method of COS with a specific degree of deacetylation that can be applied as a fertilizer.展开更多
Aim： To investigate the stage-specific localization of metastasis-associated protein 1 （MTA1） during spermatogenesis in adult human and mouse testis. Methods： The immunolocalization of MTA1 was studied by immunohi...Aim： To investigate the stage-specific localization of metastasis-associated protein 1 （MTA1） during spermatogenesis in adult human and mouse testis. Methods： The immunolocalization of MTA1 was studied by immunohistochemistry and Western blot analysis. The distribution pattern of MTA1 in mouse testis was confirmed by using quantitative analysis of purified spermatogenic cells. Results： The specificity of polyclonal antibody was confirmed by Western blot analysis. MTA1 was found expressed in the nucleus of germ cells, except elongate spermatids, and in the cytoplasm of Sertoli cells; Leydig cells did not show any specific reactivity. MTA1 possessed different distribution patterns in the two species： in humans, the most intensive staining was found in the nucleus of round spermatids and of primary spermatocytes while in mice, the most intense MTA 1 staining was in the nucleus of leptotene, zygotene and pachytene spermatocytes. In both species the staining exhibited a cyclic pattern. Conclusion： The present communication initially provides new evidence for the potential role of MTA1 in mature testis. In addition, its distinctive expression in germ cells suggests a regulatory role of the peptide during spermatogenesis.展开更多
AIM To investigate the potential effect of curcumin on hepatitis B virus(HBV) covalently closed circular DNA(ccc DNA) and the underlying mechanism.METHODS A Hep G2.2.15 cell line stably transfected with HBV was treate...AIM To investigate the potential effect of curcumin on hepatitis B virus(HBV) covalently closed circular DNA(ccc DNA) and the underlying mechanism.METHODS A Hep G2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen(HBs Ag) and e antigen(HBe Ag) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and ccc DNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound ccc DNA was detected by chromatin immunoprecipitation(Ch IP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs(si RNAs) targeting HBV were tested along with curcumin.RESULTS Curcumin treatment led to time-and dose-dependent reductions in HBs Ag and HBe Ag expression and significant reductions in intracellular HBV DNA replication intermediates and HBV ccc DNA. After treatment with 20 μmol/L curcumin for 2 d, HBs Ag and ccc DNA levels in Hep G2.2.15 cells were reduced by up to 57.7%(P < 0.01) and 75.5%(P < 0.01), respectively, compared with levels in non-treated cells. Meanwhile, time-and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3-and H4-bound ccc DNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of si RNAs targeting HBV enhanced the inhibitory effects of curcumin.CONCLUSION Curcumin inhibits HBV gene replication via downregulation of ccc DNA-bound histone acetylation and has the potential to be developed as a ccc DNA-targeting antiviral agent for hepatitis B.展开更多
文摘Chitin,distinguished by its nitrogen-rich acetamido and amino groups,imparts a distinctive cationic nature,enabling chitin to have indispensable features in various applications.Despite its significant promise in the textile industry,particularly for sustainable and functional fabric applications,the practical utilization of chitin fibers remains constrained by insufficient mechanical strength.The degree of deacetylation(DD),a key molecular-level structural determinant,has not been adequately addressed in previous studies despite its critical role in influencing chitin properties across multiple scales.In this study,a deacetylation-mediated design strategy was used to achieve enhanced mechanical performance coupled with multifunctional efficacy using an aqueous KOH/urea solution dissolution system.We prepared a series of deacetylated chitins with different DD values and systematically studied the effect of deacetylation on the multiple-scale structure of regenerated fibers,such as intermolecular interactions and chain orientation at the molecular level,and the aggregation behavior of chitin nanofibers within the gel-state and dried fibers at the micro/nano scale.To achieve an enhanced mechanical performance coupled with multifunctional efficacy by relying on an aqueous KOH/urea solution dissolution system.Moreover,deacetylation enhances intermolecular interactions,resulting in densified internal structures and improved fiber orientation.Concomitantly,it augmented the antimicrobial functionality of the fibers.This deacetylation-mediated design strategy provides a deeper understanding of the structure and properties of regenerated chitin and advances the utility of chitin in strong and sustainable fibers.
基金supported by the National Natural Science Foundation of China,Nos.81771271(to JF),81801710(to YM)the Science and Technology Project Funds from Education Department of Liaoning Province of China,Nos.LK2016022(to SZ),LK2016021(to YM)。
文摘Trans-(-)-ε-viniferin(ε-viniferin)has antioxidative and anti-inflammatory effects.It also has neuroprotective effects in Huntington's disease by activating the SIRT3/LKB1/AMPK signaling pathway;however,it remains unknown whetherε-viniferin also has a neuroprotective role in Parkinson's disease.A Parkinson's disease cell model was induced by exposing SH-SY5 Y cells to 3.0μM rotenone for 24 hours,and cells were then treated with 1.0μMε-viniferin for 24 hours.Treatment withε-viniferin upregulated SIRT3 expression,which promoted FOXO3 deacetylation and nuclear localization.ε-Viniferin also increased ATP production and decreased reactive oxygen species production.Furthermore,ε-viniferin treatment alleviated rotenone-induced mitochondrial depolarization and reduced cell apoptosis,and restored the expression of mitochondrial homeostasis-related proteins.However,when cells were transfected with SIRT3 or FOXO3 shRNA prior to rotenone andε-viniferin treatment,these changes were reversed.The results from the present study indicate thatε-viniferin enhances SIRT3-mediated FOXO3 deacetylation,reduces oxidative stress,and maintains mitochondrial homeostasis,thus inhibiting rotenone-induced cell apoptosis.ε-Viniferin may therefore be a promising treatment strategy for Parkinson's disease.
基金Supported by the National Natural Science Foundation of China(No.81170836, No.81570838)
文摘AIM: To explore the effects of IκBα SUMOylation and NF-κB p65 deacetylation on NF-κB p65 activity induced by high glucose in cultured human lens epithelial cells(HLECs).METHODS: HLECs(SRA01/04) were cultured with 5.5, 25, and 50 mmol/L glucose media for 24 h, and with 50 mmol/L glucose media for 0, 12, and 24 h respectively. SUMO1 and SIRT1 expressions were detected by reverse transcriptionpolymerase chain reaction(RT-PCR) and Western blot(WB). IκBα and NF-κB p65 expressions were detected by WB. With NAC, DTT, MG132 or Resveratrol(RSV) treatment, SUMO1 and SIRT1 expressions were detected by WB. Protein expression localizations were examined by immunofluorescence and co-immunofluorescence. The effects of SUMO1 or SIRT1 overexpression, as well as MG132 and RSV, on the nuclear expression and activity of IκBα and NF-κB p65 were analyzed by immunoblot and dual luciferase reporter gene assay.RESULTS: SUMO1 and SIRT1 expressions were influenced by high glucose in mRNA and protein levels, which could be blocked by NAC or DTT. SUMO1 was down-regulated by using MG132, and SIRT1 was up-regulated under RSV treatment. IκBα nuclear expression was attenuated and NF-κB p65 was opposite under high glucose, while IκBα and NF-κB p65 location was transferred to the nucleus. SUMO1 or SIRT1 overexpression and MG132 or RSV treatment affected the nuclear expression and activity of IκBα and NF-κB p65 under high glucose condition.CONCLUSION: IκBα SUMOylation and NF-κB p65 deacetylation affect NF-κB p65 activity in cultured HLECs under high glucose, and presumably play a significant role in controlling diabetic cataract.
基金the China"863"High-technology Development Program under contract No.2003AA625050.
文摘Chitin and chitosan films were prepared by solution casting method. Chitosan specimens used in this study were deacetylated by 50.4%, 69.2%, 85.5% and 96.3%. Their water content, protein adhesion ability, cytocompatibility, cell adhesion ability, in vitro and vivo degradability and biocompatibility were evaluated. Results indicated that with the degree of deacetylation （DD） between 50% and 70%, the chitosan showed higher water content. The higher the DD, the stronger protein adhesion ability the chitosan had. All the films have good cytocompatibility and the films with higher DD have better cell adhesion ability. Chitin films degraded more rapidly than others, which disappeared in 2 to 4 weeks after they were implanted in subcutaneous tissue and musculature. Their inflammatory reaction became weaker as the films degraded. As the DD got higher, the films degraded slower. The films of DD 85.5% and DD 90.3% even didn＇t disappeared in 12 weeks after they were implanted. Their inflammatory reaction was mild at the beginning of degradation, and became severe in 4 to 8 weeks, then weaken at last. This basic result can be very helpful for tissue engineering.
基金supported by the National Natural Science Foundation of China(Nos.21572015,21877007,81703540 and 21702007)China Postdoctoral Science Foundation(No.2018M631796)+2 种基金Technology Plan Foundation of Liaoning Province(No.20170520063)Chinese Medicine Related Scientific Research Project of Dalian(No.17Z2013)the open funding of the State Key Laboratory of Phytochemistry and Plant Resources in West China。
文摘The acetyl ester plays an important role for protection of the hydroxyl groups in carbohydrates synthesis.In the present study,we described an efficient deprotection of acetyl group of pentacyclic triterpenoid by using methanolic ammonia in THF solution.Good selectivity for cleaving gal-C2-OAc group of 3β-hydroxy-olean-12-en-28-oic acid 28-N-2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside(3) was achieved in the presence of methanolic ammonia within 4 h at low temperature(-60℃) in a yield of 56%.The reaction disclosed here provides a new method for the synthesis of C2 selective modified carbohydrates,which is more useful than conventional synthesis procedure that usually requires many steps including temporary regioselective protection and deprotection.When the reaction temperature was increased from -60℃ to room temperature,the cleavage of the other three acetyl groups of galactose in an order of C4-OAc>C3-OAc>C6-OAc was observed.Based on this study,a plausible route for the deacetylation reaction has been proposed.
基金funded by the National Natural Science Foundation of China(32130078,32441061)the National Key Research and Development Program of China(2022YFF1001604)+1 种基金Chinese Universities Scientific Fund(2024TC188)Young-scholar program of China Agricultural University-Bayannur Research Institute(2024BYNECAU009).
文摘Wheat root systems undergo dynamic and adaptive changes to mitigate adverse effects through sophisticated regulatory mechanisms under drought stress.Elucidating and utilizing these mechanisms is highly important for breeding drought-resistant wheat varieties.Here,we identify histone deacetylase TaHDA8 as a critical component that negatively regulates wheat root elongation and drought tolerance.Under drought stress,TaHDA8 could be finely tuned to alleviate its inhibition of root elongation,thereby improving wheat adaptation to water deficit.Interestingly,reduction in TaHDA8 protein levels de-represses the DNA-binding ability of TaAREB3,a positive regulator of root elongation and drought tolerance,which depends on the retention of acetylation at K248 and K281 residues.The restored DNA binding of TaAREB3 to the promoter of TaKOR1 upregulates its expression,thereby promoting root elongation by enhancing cell proliferation in the root meristem.Further studies revealed that natural variations in the TaKOR1 promoter determine the differences in TaAREB3 binding,and wheat germplasm with TaHDA8–TaAREB3–TaKOR1 regulatory module has been widely selected.Collectively,this study reveals how a lysine deacetylase regulates drought-responsive root development via non-histone deacetylation,providing genetic resources for improving root architecture and breeding drought-resilient wheat varieties.
基金supported by grants from the National Natural Science Foundation of China(32371326 and 32070551)the Science and Technology Projects in Guangzhou(E3330900-01)the Youth Innovation PromotionAssociation,CAs(201860).
文摘The shift from skotomorphogenesis to photomorphogenesis,a developmental transition in seed plants,in-volves dramatic proteomic changes.Lysine acetylation(Lys-Ac)is an evolutionarily conserved and recog-nized post-translational modification that plays a crucial role in plant development.However,its role in seedling deetiolation remains unclear.In this study,we conducted a comparative lysine acetylomic anal-ysis of etiolated Arabidopsis seedlings before and after red(R)light irradiation,uncovering that exposure to R light mainly led to protein lysine deacetylation during seedling deetiolation.Phytochrome A(phyA),a unique far-red(FR)light photoreceptor,was deacetylated at lysine 65(K65)when etiolated seedlings were moved to light.This residue is a critical ubiquitination site that regulates phyA stability.Moreover,K65 deacetylation facilitates phyA ubiquitination and 26s proteasome-mediated degradation,and is required for the function of phyA in FR light signaling and seedling photomorphogenesis.Furthermore,we identified a plant-specific lysine deacetylase HDT2 that interacts with and deacetylates phyA in the nu-cleus to promote its ubiquitination and degradation during seedling deetiolation.Genetic analysis revealed that HDT2 is critical for phyA-mediated photomorphogenic growth.Taken together,these findings reveal that lysine deacetylation of phyA by HDT2 plays a crucial role in modulating phyA turnover in response to light,suggesting that Lys-Ac might be central to the reprogramming of plants for photomorphogenic growth.
基金supported by the National Key Research and Development Program of China(2022YFA1303000,2017YFA0505602)the National Natural Science Foundation of China(81872408,81872153).
文摘The infiltration of glioblastoma multiforme(GBM)is predominantly characterized by diffuse spread,contributing significantly to therapy resistance and recurrence of GBM.In this study,we reveal that microtubule deacetylation,mediated through the downregulation of fibronectin type III and SPRY domain-containing 1(FSD1),plays a pivotal role in promoting GBM diffuse infiltration.FSD1 directly interacts with histone deacetylase 6(HDAC6)at its second catalytic domain,thereby impeding its deacetylase activity onα-tubulin and preventing microtubule deacetylation and depolymerization.This inhibitory interaction is disrupted upon phosphorylation of FSD1 at its Ser317 and Ser324 residues by activated CDK5,leading to FSD1 dissociation from microtubules and facilitating HDAC6-mediatedα-tubulin deacetylation.Furthermore,increased expression of FSD1 or interference with FSD1 phosphorylation reduces microtubule deacetylation,suppresses invasion of GBM stem cells,and ultimately mitigates tumor infiltration in orthotopic GBM xenografts.Importantly,GBM tissues exhibit diminished levels of FSD1 expression,correlating with microtubule deacetylation and unfavorable clinical outcomes in GBM patients.These findings elucidate the mechanistic involvement of microtubule deacetylation in driving GBM cell invasion and offer potential avenues for managing GBM infiltration.
文摘Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid pla- que pathogenesis in Alzheimer＇s disease （AD）. Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB （TFEB）, an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ （fAβ） degra- dation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APPIPS1 transgenic mice. Our findings reveal that deacetylaUon of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.
文摘The p53 tumor suppressor is a sequence-specific transcription factor that undergoes an abundance of post-translational modifications for its regulation and activation.Acetylation of p53 is an important reversible enzymatic process that occurs in response to DNA damage and genotoxic stress and is indispensible for p53 transcriptional activity.p53 was the first non-histone protein shown to be acetylated by histone acetyl transferases,and a number of more recent in vivo models have underscored the importance of this type of modification for p53 activity.Here,we review the current knowledge and recent findings of p53 acetylation and deacetylation and discuss the implications of these processes for the p53 pathway.
基金This work was supported by grants from the National Key Research and Development Program of China(2020YFE0202300)the Central Public-interest Scientific Institution Basal Research Fund,the BBSRC under the Grant Reference BB/P008569/1 to J.G.C.N.V.and E.dL.,and an Erasmus plus training award to L.G.
文摘In eukaryotes,histone acetylation is a major modification on histone N-terminal tails that is tightly connected to transcriptional activation.HDA6 is a histone deacetylase involved in the transcriptional regulation of genes and transposable elements(TEs)in Arabidopsis thaliana.HDA6 has been shown to participate in several complexes in plants,including a conserved SIN3 complex.Here,we uncover a novel protein complex containing HDA6,several Harbinger transposon-derived proteins(HHP1,SANT1,SANT2,SANT3,and SANT4),and MBD domain-containing proteins(MBD1,MBD2,and MBD4).We show that mutations of all four SANT genes in the sant-null mutant cause increased expression of the flowering repressors FLC,MAF4,and MAF5,resulting in a late flowering phenotype.Transcriptome deep sequencing reveals that while the SANT proteins and HDA6 regulate the expression of largely overlapping sets of genes,TE silencing is unaffected in sant-null mutants.Our global histone H3 acetylation profiling shows that SANT proteins and HDA6 modulate gene expression through deacetylation.Collectively,our findings suggest that Harbinger transposon-derived SANT domain-containing proteins are required for histone deacetylation and flowering time control in plants.
文摘TANK-binding kinase 1(TBK1),a core kinase of antiviral pathways,activates the production of interferons(IFNs).It has been reported that deacetylation activates TBK1;however,the precise mechanism still remains to be uncovered.We show here that during the early stage of viral infection,the acetylation of TBK1 was increased,and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1.HDAC3 directly deacety-lated TBK1 at Lys241 and Lys692,which resulted in the activation of TBK1.Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively.Using knockout cell lines and transgenic mice,we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs.Furthermore,activated TBK1 phosphorylated HDAC3,which promoted the deacetylation activity of HDAC3 and formed a feedback loop.In this study,we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-trans-lational modulations involved in the interaction between TBK1 and HDAC3.
文摘This paper presents experimental results on the effect of alkalis such as NaOH, KOH and Ca（OH）2 on deacetylation of a konjac glucomannan （KGM） powder under mechano-chemical （MC） treatment, The results show that the alkalinity of modifiers is a dominant factor for deacetylation of KGM, In addition, characteristics, such as swelling property, viscous stability and thermal behavior of the deacetylated KGM are analyzed
文摘In eukaryotes, nucleosome is the basic unit of chromatin. Nucleosome is composed of an octamer of histone proteins (two molecules each of histones H 2A , H 2B , H 3 and H 4) and DNA strand wound around the octamer. Some data show that core histone octamer can affect gene transcription both \%in vitro\% and \%in vivo.\% Recent results indicate that histone acetylation/deacetylation is a key step to regulate activity of genes. This article summarizes some coactivators, such as GCN5p, P300/CBP and TAF Ⅱ 250, which are recently found to have histone acetyltransferase activity. The relationship between these coactivators and gene activation is also described. Besides, this article concerns some corepressors which have histone deacetylase activity, such as Rpd3p, HDAC2. These corepressors combine with other protein complex and then repress transcription. Finally, some problems to be solved and the future direction in this active field are discussed.
文摘Production of chitosan and its derivatives by traditional methods involves the excessive use of a reaction solution comprisedof sodium hydroxide and hydrochloric acid. Waste water resulting from this process has lim让ed the application of chitosanas a fertilizer as the process causes serious environmental pollution. Specifically, the resulting waste water contains highlevels of dissolved nitrogen and minerals from shrimp shells. In this study, an eco-friendly method was established to produce chitooligosaccharides (COS) with different degrees of deacetylation (DDAs) from shrimp shell waste. At a solid-tosolventratio of 1:6, the degree of demineralization was above 90% with the treatment of 30 g-L_1 H3PO4, and the degree ofdeproteinization was above 80% when treated with 30 g-L_1 KOH at 70 °C. Chitosans with different DDAs were obtainedby microwave-assisted KOH metathesis and the COS with Mw approximately 1500 Da were then prepared by oxidativedegradation. In summary, 33.73 kg H3PO4,12.77 kg, and 241.31 kg KOH were supplied during the processes of demineralization,deproteinization, and deacetylation of 100 kg shrimp shell waste, respectively. The process water was totally recycled,demonstrating that the shrimp shell could be wholly transformed into fertilize The entire process created a product withthe fractions of N:P2O5:K2O:COS = 7.94:24.44:10.72:1 &27. The test on the germination promotion of wheat seeds revealedthat the COS with 72」2% DDA significantly promoted germination. This work demonstrated the use of an eco-friendlypreparation method of COS with a specific degree of deacetylation that can be applied as a fertilizer.
基金We are grateful to Prof. Rui-An Wang （Department of Molecular and Cellular 0ncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA） for his helpful advice and discussion regarding the pos- sible functions of MTA1. We also thank Miss Hui Wang for her careful assistance in English. This study was supported by the Natural Science Foundation of China （2006： No. 30570982 2003： No. 30370750 2003： No. 30371584）.
文摘Aim： To investigate the stage-specific localization of metastasis-associated protein 1 （MTA1） during spermatogenesis in adult human and mouse testis. Methods： The immunolocalization of MTA1 was studied by immunohistochemistry and Western blot analysis. The distribution pattern of MTA1 in mouse testis was confirmed by using quantitative analysis of purified spermatogenic cells. Results： The specificity of polyclonal antibody was confirmed by Western blot analysis. MTA1 was found expressed in the nucleus of germ cells, except elongate spermatids, and in the cytoplasm of Sertoli cells; Leydig cells did not show any specific reactivity. MTA1 possessed different distribution patterns in the two species： in humans, the most intensive staining was found in the nucleus of round spermatids and of primary spermatocytes while in mice, the most intense MTA 1 staining was in the nucleus of leptotene, zygotene and pachytene spermatocytes. In both species the staining exhibited a cyclic pattern. Conclusion： The present communication initially provides new evidence for the potential role of MTA1 in mature testis. In addition, its distinctive expression in germ cells suggests a regulatory role of the peptide during spermatogenesis.
基金Supported by National Natural Science Foundation of China,No.81541140Natural Science Foundation of Hubei province of China,No.2014CFB645+2 种基金Research and Development project of the Science and Technology plan of Hubei province,No.2011BCB030Foundation for Innovative Research Teamof Hubei University of Medicine,No.2014CXG05Key program for precision Medicine of Taihe Hospital,No.2016JZ05
文摘AIM To investigate the potential effect of curcumin on hepatitis B virus(HBV) covalently closed circular DNA(ccc DNA) and the underlying mechanism.METHODS A Hep G2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen(HBs Ag) and e antigen(HBe Ag) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and ccc DNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound ccc DNA was detected by chromatin immunoprecipitation(Ch IP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs(si RNAs) targeting HBV were tested along with curcumin.RESULTS Curcumin treatment led to time-and dose-dependent reductions in HBs Ag and HBe Ag expression and significant reductions in intracellular HBV DNA replication intermediates and HBV ccc DNA. After treatment with 20 μmol/L curcumin for 2 d, HBs Ag and ccc DNA levels in Hep G2.2.15 cells were reduced by up to 57.7%(P < 0.01) and 75.5%(P < 0.01), respectively, compared with levels in non-treated cells. Meanwhile, time-and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3-and H4-bound ccc DNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of si RNAs targeting HBV enhanced the inhibitory effects of curcumin.CONCLUSION Curcumin inhibits HBV gene replication via downregulation of ccc DNA-bound histone acetylation and has the potential to be developed as a ccc DNA-targeting antiviral agent for hepatitis B.
