Background Poor feather growth not only affects the appearance of the organism but also decreases the feed efficiency.Methionine(Met)is an essential amino acid required for feather follicle development;yet the exact m...Background Poor feather growth not only affects the appearance of the organism but also decreases the feed efficiency.Methionine(Met)is an essential amino acid required for feather follicle development;yet the exact mechanism involved remains insufficiently understood.Methods A total of 1801-day-old broilers were selected and randomly divided into 3 treatments:control group(0.45%Met),Met-deficiency group(0.25%Met),and Met-rescue group(0.45%Met in the pre-trial period and 0.25%Met in the post-trial period).The experimental period lasted for 56 d,with a pre-trial period of 1–28 d and a post-trial period of 29–56 d.In addition,Met-deficiency and Met-rescue models were constructed in feather follicle epidermal stem cell by controlling the supply of Met in the culture medium.Results Dietary Met-deficiency significantly(P<0.05)reduced the ADG,ADFI and F/G,and inhibited feather follicle development.Met supplementation significantly(P<0.05)improved growth performance and the feather growth in broilers.Met-rescue may promote feather growth in broilers by activating the Wnt/β-catenin signaling pathway(GSK-3β,CK1,Axin1,β-catenin,Activeβ-catenin,TCF4,and Cyclin D1).Compared with Met-deficiency group,Met-rescue significantly(P<0.05)increased the activity of feather follicle epidermal stem cell and mitochondrial membrane potential,activated Wnt/β-catenin signaling pathway,and decreased the content of reactive oxygen species(P<0.05).CO-IP confirmed that mitochondrial protein PGAM5 interacted with Axin1,the scaffold protein of the disruption complex of the Wnt/β-catenin signaling pathway,and directly mediated Met regulation of Wnt/β-catenin signaling pathway and feather follicle development.Conclusions PGAM5 binding to Axin1 mediates the regulation of Wnt/β-catenin signaling pathway,and promotes feather follicle development and feather growth of broiler chickens through Met supplementation.These results provide theoretical support for the improvement of economic value and production efficiency of broiler chickens.展开更多
Methionine,an essential amino acid,is abundant in animal protein.High dietary methionine intake is associated with the promotion of colorectal cancer(CRC);however,the mechanisms remain unclear.This study aimed to inve...Methionine,an essential amino acid,is abundant in animal protein.High dietary methionine intake is associated with the promotion of colorectal cancer(CRC);however,the mechanisms remain unclear.This study aimed to investigate the underlying mechanisms of high dietary methionine promoting CRC and evaluate the effect of high dietary methionine on healthy intestine.Our results demonstrated that high dietary methionine intake exhibited a higher incidence and invasion of tumors in azoxymethane/dextran sulfate sodium-induced mice.Meanwhile,the gut microbiota were disturbed,consequently fostering the metabolism of secondary bile acids.The contents of lithocholic acid and deoxycholic acid significantly increased(P<0.01),which further activated the bile acid membrane receptors TGR5,and then the activated TGR5 promoted tumor proliferation through STAT3 and YAP pathways.Pseudo-germ-free mice validated the role of gut microbiota and secondary bile acids in promoting CRC by high dietary methionine.Notably,similar disturbances in gut microbiota and bile acid metabolism were observed in the intestine of healthy mice with high dietary methionine intake.In conclusion,dysregulation of bile acid metabolism and activation of the corresponding receptor TGR5 were mechanisms promoting CRC associated with high dietary methionine intake.展开更多
Background:With the increasing risk of nuclear exposure,more attention has been paid to the prevention and treatment of acute radiation syndrome(ARS).Although amino acids are key nutrients involved in hematopoietic re...Background:With the increasing risk of nuclear exposure,more attention has been paid to the prevention and treatment of acute radiation syndrome(ARS).Although amino acids are key nutrients involved in hematopoietic regulation,the impacts of amino acids on bone marrow hematopoiesis following irradiation and the associated mechanisms have not been fully elucidated.Hence,it is of paramount importance to study the changes in amino acid metabolism after irradiation and their effects on hematopoiesis as well as the related mechanisms.Methods:The content of serum amino acids was analyzed using metabolomic sequencing.The survival rate and body weight of the irradiated mice were detected after altering the methionine content in the diet.Extracellular matrix(ECM)protein analysis was performed via proteomics analysis.Inflammatory factors were examined by enzyme-linked immunosorbent assay(ELISA).Flow cytometry,Western blotting,and immunofluorescence were employed to determine the mechanism by which S100 calcium-binding protein A4(S100A4)regulates macrophage polarization.Results:The survival time of irradiated mice was significantly associated with alterations in multiple amino acids,particularly methionine.A high methionine diet promoted irradiation tolerance,especially in the recovery of bone marrow hematopoiesis,yet with dose limitations.Folate metabolism could partially alleviate the dose bottleneck by reducing the accumulation of homocysteine.Mechanistically,high methionine levels maintained the abundance of ECM components,including collagens and glycoproteins,in the bone marrow post-irradiation,among which the level of S100A4 was significantly changed.S100A4 regulated macrophage polarization via the STAT3 pathway,inhibited bone marrow inflammation and facilitated the proliferation and differentiation of hematopoietic stem/progenitor cells.Conclusions:We have demonstrated that an appropriate elevation in dietary methionine enhances irradiation tolerance in mice and explains the mechanism by which methionine regulates bone marrow hematopoiesis after irradiation.展开更多
A variant cell line of Medicago saliva L. resistant to methionine (100 mmol/L) was selected .from calli treated with 1.5 mmol/L sodium azide. Plants were regenerated from this selected cell line. After growing for 6 m...A variant cell line of Medicago saliva L. resistant to methionine (100 mmol/L) was selected .from calli treated with 1.5 mmol/L sodium azide. Plants were regenerated from this selected cell line. After growing for 6 months on the medium devoid of selection pressure, the variant cell line still showed high level of resistance, which was 7.2-fold higher than that of the wild type. This indicated the stability of the resistance expression. The variant cell line also expressed a 3.3-fold higher cross-resistance to ethionine, than that of the wild type. The contents of methionine, lysine, threonine and isoleucine in the variant calli were respectively 2.0, 1.43, 1.71 and 1.57 times higher than those in the wild type. However, in the variant regenerated plantlets they respectively were 2.0, 1.33, 1.22 and 1.22 times higher than those in the wild type regenerants. Four new protein bands, viz. 65 kD, 23 kD, 20 kD and 18 kD, appeared in the SDS-PAGE pattern of soluble proteins in the variant calli. In the peroxidase isoenzyme electrophoresis pattern, two new bands were also observed in the variant calli.展开更多
[Objective] The mRNA expression level changes of S-adenosylmethionine synthetase （SAMS） under low temperature stress was studied. [Method] Total RNA were extracted from leaves, stem and earthnut of sweet potato 0,12...[Objective] The mRNA expression level changes of S-adenosylmethionine synthetase （SAMS） under low temperature stress was studied. [Method] Total RNA were extracted from leaves, stem and earthnut of sweet potato 0,12,24,48 and 72 h after low temperature treatement, mRNA expression level was analyzed by reverse expression and Real-time PCR technique. [Result] The expression quality of the gene extracted from leaves, stem and earthnut increased and the expression quality reached the peak point 24,72 and 72 h after low temperature treatment respectively. The expression change of earthnut was the biggest. [Conclusion] Low temperature was good for increasing mRNA expression of relevart genes.展开更多
为了探究过瘤胃蛋氨酸(Rumen-protected methionine,RPM)对泌乳高峰期奶牛生产性能和全肠道消化率的影响,试验选取16头处于泌乳高峰期,体重、生理状况相似的健康荷斯坦奶牛,随机分为2组。对照组每日饲喂基础TMR日粮,RPM组每头牛在基础...为了探究过瘤胃蛋氨酸(Rumen-protected methionine,RPM)对泌乳高峰期奶牛生产性能和全肠道消化率的影响,试验选取16头处于泌乳高峰期,体重、生理状况相似的健康荷斯坦奶牛,随机分为2组。对照组每日饲喂基础TMR日粮,RPM组每头牛在基础日粮的基础上,每日单独补饲15 g RPM。结果表明:(1)泌乳高峰期奶牛日粮中添加RPM不影响体重、体况评分和干物质采食量(DMI)(P>0.05);(2)添加RPM对奶牛的产奶量和乳成分影响不显著(P>0.05);(3)添加RPM有降低瘤胃丁酸含量的趋势(P=0.069);(4)添加RPM不影响奶牛的表观消化率(P>0.05);(5)RPM显著提高了奶牛血浆尿素氮和二氧化碳水平(P<0.05);(6)RPM对血液中蛋氨酸的含量没有影响,脯氨酸浓度显著降低(P<0.05),具有降低血浆精氨酸和天冬氨酸含量的趋势(0.05<P<0.10)。总体而言,泌乳高峰期奶牛补饲RPM可能通过提高蛋氨酸吸收率、氨基酸代谢和机体蛋白合成改善泌乳高峰期奶牛健康状况。展开更多
AIM To investigate the interference ofmethionine.free parenteral nutrition plus 5-Fu（-MetTPN+5-Fu）in gastric cancer cell kineticsand the side effects of the regimen.METHODS Fifteen patients with advancedgastric canc...AIM To investigate the interference ofmethionine.free parenteral nutrition plus 5-Fu（-MetTPN+5-Fu）in gastric cancer cell kineticsand the side effects of the regimen.METHODS Fifteen patients with advancedgastric cancer were randomly divided into twogroups,7 patients were given preoperatively aseven-day course of standard parenteralnutrition in combination with a five-day courseof chemotherapy（sTPN+5-Fu）,while the other8 patients were given methionine-deprivedparenteral nutrition and 5-Fu（-MetTPN+5-Fu）.Cell cycles of gastric cancer and normal mucosawere studied by flow cytometry（FCM）.Bloodsamples were taken to measure the serumprotein,methionine（Met）and cysteine（Cys）levels,and liver and kidney functions.RESULTS As compared with the resultsobtained before the treatment,the percentage ofG<sub>0</sub>/G<sub>1</sub> tumor cells increased and that of S phasedecreased in the-MetTPN+5-Fu group,while thecontrary was observed in the sTPN+5-Fu group.Except that the ALT,AST and AKP levels wereslightly increased in a few cases receiving-MetTPN+5-Fu,all the other biochemicalparameters were within normal limits.Serum Cys level decreased slightly after the treatmentin both groups.Serum Met level of patientsreceiving sTPN+5-Fu was somewhat higher aftertreatment than that before treatment;however,no significant change occurred in the -MetTPN+5-Fu group,nor operative complications in bothgroups.CONCLUSION -MetTPN+5-Fu exerted asuppressive effect on cancer cell proliferation,probably through a double mechanism ofcreating a state of'Met starvation'adverse tothe tumor cell cycle,and by allowing 5-Fu to killspecifically cells in S phase.Preoperative short-term administration of -MetTPN+5-Fu had littleundesirable effect on host metabolism.展开更多
After the application of methionine, a progressive and significant increase occurred in five volatile organic sulfur compounds （VOSCs）： methanethiol （MESH）, dimethyl sulfide （DMS）, dime^yl disulfide （DMDS）, d...After the application of methionine, a progressive and significant increase occurred in five volatile organic sulfur compounds （VOSCs）： methanethiol （MESH）, dimethyl sulfide （DMS）, dime^yl disulfide （DMDS）, dimethyl trisulfide （DMTS） and dimethyl tetrasulfide （DMTeS）. Even in the untreated control without a methionine addition, methionine and its catabolites （VOSCs, mainly DMDS） were found in considerable amounts that were high enough to account for the water＇s offensive odor. However, blackening only occurred in two methionine-amended treatments. The VOSCs production was observed to precede black color development, and the reaching of a peak value for total VOSCs was often followed by water blackening. The presence of glucose stimulated the degradation of methionine while postponing the occurrence of the black color and inhibiting the production of VOSCs. In addition, DMDS was found to be the most abundant species produced after the addition of methionine alone, and DMTeS appeared to be the most important compound produced after the addition of methionine＋glucose. These results suggest that methionine acted as an important precursor of the VOSCs in lakes suffering from algea-induced black bloom. The existence of glucose may change the transformation pathway of methionine into VOSCs to form larger molecular weight compounds, such as DMTS and DMTeS.展开更多
AIM: To elucidate whether human primary gastric cancer and gastric mucosa epithelial cells in vitro can grow normally in a methionine (Met) depleted environment, i.e. Met-dependence, and whether Met-depleting status c...AIM: To elucidate whether human primary gastric cancer and gastric mucosa epithelial cells in vitro can grow normally in a methionine (Met) depleted environment, i.e. Met-dependence, and whether Met-depleting status can enhance the killing effect of chemotherapy on gastric cancer cells. METHODS: Fresh human gastric cancer and mucosal tissues were managed to form monocellular suspensions, which were then cultured in the Met-free but homocysteine-containing (Met(-)Hcy(+)) medium, with different chemotherapeutic drugs. The proliferation of the cells was examined by cell counter, flow cytometry (FCM) and microcytotoxicity assay (MTT). RESULTS: The growth of human primary gastric cancer cells in Met(-)Hcy(+) was suppressed, manifested by the decrease of total cell counts [1.46 +/- 0.42 (x 10(9).L(-1)) in Met(-)Hcy(+) vs 1.64 +/-0.44(x 10(9).L(-1)) in Met(+)Hcy(-), P【0.01], the decline in the percentage of G(0)G(1) phase cells (0.69 +/- 0.24 in Met(-)Hcy(+) vs 0.80 +/- 0.18 in Met(+)Hcy(-), P【0.01) and the increase of S cells (0.24 +/- 0.20 in Met(-)Hcy(+) vs 0.17 +/- 0.16 in Met(+)Hcy(-), P【0.01); however, gastric mucosal cells grew normally. If Met(-)Hcy(+) medium was used in combination with chemotherapeutic drugs, the number of surviving gastric cancer cells dropped significantly. CONCLUSION: Human primary gastric cancer cells in vitro are Met-dependent; however, gastric mucosal cells have not shown the same characteristics. Met(-)Hcy(+) environment may strengthen the killing effect of chemotherapy on human primary gastric cancer cells.展开更多
Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express...Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express two genes,MAT1A and MAT2A,which encode for MATα1 and MATα2,the catalytic subunits of the MAT isoenzymes,respectively.A third gene MAT2B,encodes a regulatory subunit known as MATβwhich controls the activity of MATα2.MAT1A,which is mainly expressed in hepatocytes,maintains the differentiated state of these cells,whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver(e.g.,hepatic stellate and Kupffer cells).The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1.A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation,but this change in the expression pattern of MATs results in reduced hepatic SAMe level.Decades of study have utilized the Mat1a-knockout(KO)mouse that spontaneously develops non-alcoholic steatohepatitis(NASH)and hepatocellular carcinoma(HCC)to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver carcinogenesis.An increasing volume of work indicates that MATs have SAMe-independent functions,distinct interactomes and multiple subcellular localizations.Here we aim to provide an overview of MAT biology including genes,isoenzymes and their regulation to provide the context for understanding consequences of their dysregulation.We will highlight recent breakthroughs in the field and underscore the importance of MAT’s in liver tumorigenesis as well as their potential as targets for cancer therapy.展开更多
Background: Methionine is an essential amino acid for fish. The present study was conducted to investigate the effects of dietary methionine on growth performance, digestive and absorptive ability, as well as antioxid...Background: Methionine is an essential amino acid for fish. The present study was conducted to investigate the effects of dietary methionine on growth performance, digestive and absorptive ability, as well as antioxidant capacity in the intestine and hepatopancreas of sub-adult grass carp(Ctenopharyngodon idella).Results: Dietary methionine deficiency significantly decreased percentage weight gain(PWG), feed intake, feed efficiency and protein efficiency ratio, as well as activities of hepatopancreatic glutamate-oxaloacetate transaminase and muscle glutamate-pyruvate transaminase in sub-adult grass carp(P < 0.05). Furthermore, methionine deficiency significantly reduced activities of trypsin, lipase and amylase in the intestine, Na^+/K^+-ATPase, alkaline phosphatase and γ-glutamyl transpeptidase in three intestinal segments, and creatine kinase(CK) in the proximal intestine(P < 0.05). However, an unexplained and significant increase in CK activity in the mid intestine was associated with dietary methionine deficiency. Malondialdehyde and protein carbonyl contents in the intestine and hepatopancreas were significantly increased by methionine deficiency(P < 0.05), whereas anti-hydroxyl radical capacity in the hepatopancreas and intestine, and anti-superoxide anion capacity in the intestine, were significantly decreased by methionine deficiency(P < 0.05). Moreover, methionine deficiency significantly decreased superoxide dismutase and glutathione reductase activities, glutathione contents in the hepatopancreas and intestine, as well as glutathione peroxidase activity in the intestine(P < 0.05), whereas it significantly increased activities of catalase in the hepatopancreas and glutathione-S-transferase in the hepatopancreas and intestine(P < 0.05).(Continued on next page)(Continued from previous page)Conclusions: The present results demonstrated that dietary methionine deficiency induced poor growth, and decreased digestive and absorptive function and antioxidant capacity in the hepatopancreas and intestine of sub-adult grass carp. Methionine requirements for sub-adult grass carp(450-1, 170 g) based on PWG, intestinal trypsin, and hepatopancreatic anti-hydroxyl radical activities were estimated to be 6.12 g/kg diet(21.80 g/kg protein),6.99 g/kg diet(24.90 g/kg protein) and 5.42 g/kg diet(19.31 g/kg protein), respectively, in the presence of 1.50 g cysteine/kg(5.35 g/kg protein).展开更多
AIM: To investigate the influence of L-methionine-deprived total parenteral nutrition with 5-FU on gastric cancer and host metabolism. METHODS: N-methyl-N'-nitro-nitrosoguanidine (MNNG) induced gastric cancer rats...AIM: To investigate the influence of L-methionine-deprived total parenteral nutrition with 5-FU on gastric cancer and host metabolism. METHODS: N-methyl-N'-nitro-nitrosoguanidine (MNNG) induced gastric cancer rats were randomly divided into four groups: Met-containing TPN group (n=11), Met-deprived TPN group (n =12), Met-containing TPN+5-FU group (n=11) and Met-deprived TPN+5-FU group (n=12). Five rats in each group were sacrificed after 7 days of treatment and the samples were taken for examination. The remaining rats in each group were then fed separately with normal diet after the treatment until death, the life span was noted. RESULTS: The tumors were enlarged in Met-containing group and shrank in Met-deprived group markedly after the treatment. The DNA index (DI) of tumor cells and the body weight (BW) of rats had no significant change in the two groups, however, the ratio of tumor cells'S phase was increased. The ratio of G2M phase went up in Met-containing group, but down in Met-deprived group. In the other two groups that 5-FU was added, the BW of rats, and the diameter of tumors, the DI of tumor cells, the S and G2M phase ratio of tumor cells were all decreased, particularly in Met-deprived plus 5-FU group. Pathological examination revealed that the necrotic foci of the tumor tissue increased after Met-deprived TPN treatment, and the nucleoli of tumor cells enlarged. In MetTPN+5-FU group, severe nuclear damage was also found by karyopyknosis and karyorrhexis, meanwhile there was slight degeneration in some liver and kidney cells. The serum free Met and Cysteine decreased markedly (P【0.001), while other amino acids, such as serum free serine and glutamine increased significantly (P【0.005). All the rats died of multiple organ failure caused by cancer metastasis. The average survival time was 18.6 days in Met-containing TPN group, 31 days in Met-deprived TPN group, 27.5 days in Met-containing TPN+5-FU group, and 43 days in Met-deprived TPN+5-FU group (P【0.05). CONCLUSION: Met-deprived TPN causes methionine starvation of tumor cells, and can enhance the anti-tumor effect of 5-FU and prolong the life span of gastric cancer bearing rats.展开更多
The purpose of this study was to investigate the effects of methionine deficiency on cellular immune function by determining morphological and ultrastructural changes of thymus, thymic cell cycle and apoptosis, periph...The purpose of this study was to investigate the effects of methionine deficiency on cellular immune function by determining morphological and ultrastructural changes of thymus, thymic cell cycle and apoptosis, peripheral blood T-cell subsets, T- cell proliferation function and the serum interleukin-2 （IL-2） contents. 120 1-d-old broilers were randomly divided into two groups （6 replicates in each group and l0 broilers in each replicate） and fed on a control diet or methionine deficient diet for 42 d. Lesions were observed in experiment. Histopathologically, lymphopenia and congestion were observed in the medulla of thymic lobule. Ultrastructurally, there were more apoptosis lymphocytes, and the mitochondria of lymphocytes were swelled in thymus of methionine deficiency. The G0/G~ phase of the cell cycle of the thymus was much higher （P〈0.01）, and the S, G2＋M phases and proliferating index （PI） were lower （P〈0.01） in methionine deficiency than in control group. And the percentage of apoptotic cells in the thymus was significantly increased in methionine deficiency （P〈0.01）. The percentage of CD4＋ and CD8~ T-cells was decreased in methionine deficiency compared with control group. Meanwhile, the proliferation function of peripheral blood T-cell was decreased in methionine deficiency. Also, the serum IL-2 contents were decreased in methionine deficiency. It was concluded that methionine deficiency could cause pathological and ultrastructural changes of thymus, reduce the T-cell population, serum IL-2 contents and the proliferation function of T- cells, and induce increased percentage of apoptotic cells. The cellular immune function was finally impaired in broilers.展开更多
基金supported by the National Natural Science Foundation of China(32372902)Guangdong Special Support Program for Young Talents(NYQN2024007)。
文摘Background Poor feather growth not only affects the appearance of the organism but also decreases the feed efficiency.Methionine(Met)is an essential amino acid required for feather follicle development;yet the exact mechanism involved remains insufficiently understood.Methods A total of 1801-day-old broilers were selected and randomly divided into 3 treatments:control group(0.45%Met),Met-deficiency group(0.25%Met),and Met-rescue group(0.45%Met in the pre-trial period and 0.25%Met in the post-trial period).The experimental period lasted for 56 d,with a pre-trial period of 1–28 d and a post-trial period of 29–56 d.In addition,Met-deficiency and Met-rescue models were constructed in feather follicle epidermal stem cell by controlling the supply of Met in the culture medium.Results Dietary Met-deficiency significantly(P<0.05)reduced the ADG,ADFI and F/G,and inhibited feather follicle development.Met supplementation significantly(P<0.05)improved growth performance and the feather growth in broilers.Met-rescue may promote feather growth in broilers by activating the Wnt/β-catenin signaling pathway(GSK-3β,CK1,Axin1,β-catenin,Activeβ-catenin,TCF4,and Cyclin D1).Compared with Met-deficiency group,Met-rescue significantly(P<0.05)increased the activity of feather follicle epidermal stem cell and mitochondrial membrane potential,activated Wnt/β-catenin signaling pathway,and decreased the content of reactive oxygen species(P<0.05).CO-IP confirmed that mitochondrial protein PGAM5 interacted with Axin1,the scaffold protein of the disruption complex of the Wnt/β-catenin signaling pathway,and directly mediated Met regulation of Wnt/β-catenin signaling pathway and feather follicle development.Conclusions PGAM5 binding to Axin1 mediates the regulation of Wnt/β-catenin signaling pathway,and promotes feather follicle development and feather growth of broiler chickens through Met supplementation.These results provide theoretical support for the improvement of economic value and production efficiency of broiler chickens.
基金financially supported by the National Natural Science Foundation of China(32001795)。
文摘Methionine,an essential amino acid,is abundant in animal protein.High dietary methionine intake is associated with the promotion of colorectal cancer(CRC);however,the mechanisms remain unclear.This study aimed to investigate the underlying mechanisms of high dietary methionine promoting CRC and evaluate the effect of high dietary methionine on healthy intestine.Our results demonstrated that high dietary methionine intake exhibited a higher incidence and invasion of tumors in azoxymethane/dextran sulfate sodium-induced mice.Meanwhile,the gut microbiota were disturbed,consequently fostering the metabolism of secondary bile acids.The contents of lithocholic acid and deoxycholic acid significantly increased(P<0.01),which further activated the bile acid membrane receptors TGR5,and then the activated TGR5 promoted tumor proliferation through STAT3 and YAP pathways.Pseudo-germ-free mice validated the role of gut microbiota and secondary bile acids in promoting CRC by high dietary methionine.Notably,similar disturbances in gut microbiota and bile acid metabolism were observed in the intestine of healthy mice with high dietary methionine intake.In conclusion,dysregulation of bile acid metabolism and activation of the corresponding receptor TGR5 were mechanisms promoting CRC associated with high dietary methionine intake.
基金supported by the National Natural Science Foundation of China(82020108025,82022061)the Chongqing Natural Science Foundation(cstc2021jcyj-jqX0004,cstb2022nscq-msx0179)the Clinical Research Funding of the Second Affiliated Hospital of the Army Medical(2023XKRC008,2022YQB010).
文摘Background:With the increasing risk of nuclear exposure,more attention has been paid to the prevention and treatment of acute radiation syndrome(ARS).Although amino acids are key nutrients involved in hematopoietic regulation,the impacts of amino acids on bone marrow hematopoiesis following irradiation and the associated mechanisms have not been fully elucidated.Hence,it is of paramount importance to study the changes in amino acid metabolism after irradiation and their effects on hematopoiesis as well as the related mechanisms.Methods:The content of serum amino acids was analyzed using metabolomic sequencing.The survival rate and body weight of the irradiated mice were detected after altering the methionine content in the diet.Extracellular matrix(ECM)protein analysis was performed via proteomics analysis.Inflammatory factors were examined by enzyme-linked immunosorbent assay(ELISA).Flow cytometry,Western blotting,and immunofluorescence were employed to determine the mechanism by which S100 calcium-binding protein A4(S100A4)regulates macrophage polarization.Results:The survival time of irradiated mice was significantly associated with alterations in multiple amino acids,particularly methionine.A high methionine diet promoted irradiation tolerance,especially in the recovery of bone marrow hematopoiesis,yet with dose limitations.Folate metabolism could partially alleviate the dose bottleneck by reducing the accumulation of homocysteine.Mechanistically,high methionine levels maintained the abundance of ECM components,including collagens and glycoproteins,in the bone marrow post-irradiation,among which the level of S100A4 was significantly changed.S100A4 regulated macrophage polarization via the STAT3 pathway,inhibited bone marrow inflammation and facilitated the proliferation and differentiation of hematopoietic stem/progenitor cells.Conclusions:We have demonstrated that an appropriate elevation in dietary methionine enhances irradiation tolerance in mice and explains the mechanism by which methionine regulates bone marrow hematopoiesis after irradiation.
基金This research project was supported by the National Natural Science Foundation of China.
文摘A variant cell line of Medicago saliva L. resistant to methionine (100 mmol/L) was selected .from calli treated with 1.5 mmol/L sodium azide. Plants were regenerated from this selected cell line. After growing for 6 months on the medium devoid of selection pressure, the variant cell line still showed high level of resistance, which was 7.2-fold higher than that of the wild type. This indicated the stability of the resistance expression. The variant cell line also expressed a 3.3-fold higher cross-resistance to ethionine, than that of the wild type. The contents of methionine, lysine, threonine and isoleucine in the variant calli were respectively 2.0, 1.43, 1.71 and 1.57 times higher than those in the wild type. However, in the variant regenerated plantlets they respectively were 2.0, 1.33, 1.22 and 1.22 times higher than those in the wild type regenerants. Four new protein bands, viz. 65 kD, 23 kD, 20 kD and 18 kD, appeared in the SDS-PAGE pattern of soluble proteins in the variant calli. In the peroxidase isoenzyme electrophoresis pattern, two new bands were also observed in the variant calli.
文摘[Objective] The mRNA expression level changes of S-adenosylmethionine synthetase （SAMS） under low temperature stress was studied. [Method] Total RNA were extracted from leaves, stem and earthnut of sweet potato 0,12,24,48 and 72 h after low temperature treatement, mRNA expression level was analyzed by reverse expression and Real-time PCR technique. [Result] The expression quality of the gene extracted from leaves, stem and earthnut increased and the expression quality reached the peak point 24,72 and 72 h after low temperature treatment respectively. The expression change of earthnut was the biggest. [Conclusion] Low temperature was good for increasing mRNA expression of relevart genes.
文摘为了探究过瘤胃蛋氨酸(Rumen-protected methionine,RPM)对泌乳高峰期奶牛生产性能和全肠道消化率的影响,试验选取16头处于泌乳高峰期,体重、生理状况相似的健康荷斯坦奶牛,随机分为2组。对照组每日饲喂基础TMR日粮,RPM组每头牛在基础日粮的基础上,每日单独补饲15 g RPM。结果表明:(1)泌乳高峰期奶牛日粮中添加RPM不影响体重、体况评分和干物质采食量(DMI)(P>0.05);(2)添加RPM对奶牛的产奶量和乳成分影响不显著(P>0.05);(3)添加RPM有降低瘤胃丁酸含量的趋势(P=0.069);(4)添加RPM不影响奶牛的表观消化率(P>0.05);(5)RPM显著提高了奶牛血浆尿素氮和二氧化碳水平(P<0.05);(6)RPM对血液中蛋氨酸的含量没有影响,脯氨酸浓度显著降低(P<0.05),具有降低血浆精氨酸和天冬氨酸含量的趋势(0.05<P<0.10)。总体而言,泌乳高峰期奶牛补饲RPM可能通过提高蛋氨酸吸收率、氨基酸代谢和机体蛋白合成改善泌乳高峰期奶牛健康状况。
基金the National Natural Science Foundation of China,No.39370780
文摘AIM To investigate the interference ofmethionine.free parenteral nutrition plus 5-Fu（-MetTPN+5-Fu）in gastric cancer cell kineticsand the side effects of the regimen.METHODS Fifteen patients with advancedgastric cancer were randomly divided into twogroups,7 patients were given preoperatively aseven-day course of standard parenteralnutrition in combination with a five-day courseof chemotherapy（sTPN+5-Fu）,while the other8 patients were given methionine-deprivedparenteral nutrition and 5-Fu（-MetTPN+5-Fu）.Cell cycles of gastric cancer and normal mucosawere studied by flow cytometry（FCM）.Bloodsamples were taken to measure the serumprotein,methionine（Met）and cysteine（Cys）levels,and liver and kidney functions.RESULTS As compared with the resultsobtained before the treatment,the percentage ofG<sub>0</sub>/G<sub>1</sub> tumor cells increased and that of S phasedecreased in the-MetTPN+5-Fu group,while thecontrary was observed in the sTPN+5-Fu group.Except that the ALT,AST and AKP levels wereslightly increased in a few cases receiving-MetTPN+5-Fu,all the other biochemicalparameters were within normal limits.Serum Cys level decreased slightly after the treatmentin both groups.Serum Met level of patientsreceiving sTPN+5-Fu was somewhat higher aftertreatment than that before treatment;however,no significant change occurred in the -MetTPN+5-Fu group,nor operative complications in bothgroups.CONCLUSION -MetTPN+5-Fu exerted asuppressive effect on cancer cell proliferation,probably through a double mechanism ofcreating a state of'Met starvation'adverse tothe tumor cell cycle,and by allowing 5-Fu to killspecifically cells in S phase.Preoperative short-term administration of -MetTPN+5-Fu had littleundesirable effect on host metabolism.
基金supported by the National Natural Science Foundation of China (No. 50979102, 40730528,40901252, 20907057)
文摘After the application of methionine, a progressive and significant increase occurred in five volatile organic sulfur compounds （VOSCs）： methanethiol （MESH）, dimethyl sulfide （DMS）, dime^yl disulfide （DMDS）, dimethyl trisulfide （DMTS） and dimethyl tetrasulfide （DMTeS）. Even in the untreated control without a methionine addition, methionine and its catabolites （VOSCs, mainly DMDS） were found in considerable amounts that were high enough to account for the water＇s offensive odor. However, blackening only occurred in two methionine-amended treatments. The VOSCs production was observed to precede black color development, and the reaching of a peak value for total VOSCs was often followed by water blackening. The presence of glucose stimulated the degradation of methionine while postponing the occurrence of the black color and inhibiting the production of VOSCs. In addition, DMDS was found to be the most abundant species produced after the addition of methionine alone, and DMTeS appeared to be the most important compound produced after the addition of methionine＋glucose. These results suggest that methionine acted as an important precursor of the VOSCs in lakes suffering from algea-induced black bloom. The existence of glucose may change the transformation pathway of methionine into VOSCs to form larger molecular weight compounds, such as DMTS and DMTeS.
基金the Science Foundation of Ministry of Health of China,No.96-2-296
文摘AIM: To elucidate whether human primary gastric cancer and gastric mucosa epithelial cells in vitro can grow normally in a methionine (Met) depleted environment, i.e. Met-dependence, and whether Met-depleting status can enhance the killing effect of chemotherapy on gastric cancer cells. METHODS: Fresh human gastric cancer and mucosal tissues were managed to form monocellular suspensions, which were then cultured in the Met-free but homocysteine-containing (Met(-)Hcy(+)) medium, with different chemotherapeutic drugs. The proliferation of the cells was examined by cell counter, flow cytometry (FCM) and microcytotoxicity assay (MTT). RESULTS: The growth of human primary gastric cancer cells in Met(-)Hcy(+) was suppressed, manifested by the decrease of total cell counts [1.46 +/- 0.42 (x 10(9).L(-1)) in Met(-)Hcy(+) vs 1.64 +/-0.44(x 10(9).L(-1)) in Met(+)Hcy(-), P【0.01], the decline in the percentage of G(0)G(1) phase cells (0.69 +/- 0.24 in Met(-)Hcy(+) vs 0.80 +/- 0.18 in Met(+)Hcy(-), P【0.01) and the increase of S cells (0.24 +/- 0.20 in Met(-)Hcy(+) vs 0.17 +/- 0.16 in Met(+)Hcy(-), P【0.01); however, gastric mucosal cells grew normally. If Met(-)Hcy(+) medium was used in combination with chemotherapeutic drugs, the number of surviving gastric cancer cells dropped significantly. CONCLUSION: Human primary gastric cancer cells in vitro are Met-dependent; however, gastric mucosal cells have not shown the same characteristics. Met(-)Hcy(+) environment may strengthen the killing effect of chemotherapy on human primary gastric cancer cells.
基金National Institutes of Health,NIAAA,No.R01AA026759(Lu)National Institutes of Health,NIDDK,No.R01DK107288(Lu)+4 种基金National Institutes of Health,NCCIH,No.R01AT001576National Institutes of Health,NCI,No.R01CA172086(Lu and Mato)Agencia Estatal de Investigación MINECO,No.SAF 2017-88041-RISCiii PIE14/00031,No.CIBERehdISCiiiSevero Ochoa Excellence Accreditation,No.SEV-2016-0644)(Mato)
文摘Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express two genes,MAT1A and MAT2A,which encode for MATα1 and MATα2,the catalytic subunits of the MAT isoenzymes,respectively.A third gene MAT2B,encodes a regulatory subunit known as MATβwhich controls the activity of MATα2.MAT1A,which is mainly expressed in hepatocytes,maintains the differentiated state of these cells,whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver(e.g.,hepatic stellate and Kupffer cells).The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1.A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation,but this change in the expression pattern of MATs results in reduced hepatic SAMe level.Decades of study have utilized the Mat1a-knockout(KO)mouse that spontaneously develops non-alcoholic steatohepatitis(NASH)and hepatocellular carcinoma(HCC)to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver carcinogenesis.An increasing volume of work indicates that MATs have SAMe-independent functions,distinct interactomes and multiple subcellular localizations.Here we aim to provide an overview of MAT biology including genes,isoenzymes and their regulation to provide the context for understanding consequences of their dysregulation.We will highlight recent breakthroughs in the field and underscore the importance of MAT’s in liver tumorigenesis as well as their potential as targets for cancer therapy.
基金supported by the National Basic Research Program of China(973 Program)(2014CB138600)National Science Foundation of China(31502184)+7 种基金Outstanding Talents and Innovative Team of Agricultural Scientific Research(Ministry of Agriculture)the National Department Public Benefit Research Foundation(Agriculture)of China(201003020)the Specialized Research Fund for the Doctoral Program of Higher Education of China(20135103110001)Science and Technology Support Program of Sichuan Province of China(2014NZ0003)Major Scientific and Technological Achievement Transformation Project of Sichuan Province of China(2012NC00072013NC0045)the Demonstration of Major Scientific and Technological Achievement Transformation Project of Sichuan Province of China(2015CC0011)Natural Science Foundation for Young Scientists of Sichuan Province(2014JQ0007)
文摘Background: Methionine is an essential amino acid for fish. The present study was conducted to investigate the effects of dietary methionine on growth performance, digestive and absorptive ability, as well as antioxidant capacity in the intestine and hepatopancreas of sub-adult grass carp(Ctenopharyngodon idella).Results: Dietary methionine deficiency significantly decreased percentage weight gain(PWG), feed intake, feed efficiency and protein efficiency ratio, as well as activities of hepatopancreatic glutamate-oxaloacetate transaminase and muscle glutamate-pyruvate transaminase in sub-adult grass carp(P < 0.05). Furthermore, methionine deficiency significantly reduced activities of trypsin, lipase and amylase in the intestine, Na^+/K^+-ATPase, alkaline phosphatase and γ-glutamyl transpeptidase in three intestinal segments, and creatine kinase(CK) in the proximal intestine(P < 0.05). However, an unexplained and significant increase in CK activity in the mid intestine was associated with dietary methionine deficiency. Malondialdehyde and protein carbonyl contents in the intestine and hepatopancreas were significantly increased by methionine deficiency(P < 0.05), whereas anti-hydroxyl radical capacity in the hepatopancreas and intestine, and anti-superoxide anion capacity in the intestine, were significantly decreased by methionine deficiency(P < 0.05). Moreover, methionine deficiency significantly decreased superoxide dismutase and glutathione reductase activities, glutathione contents in the hepatopancreas and intestine, as well as glutathione peroxidase activity in the intestine(P < 0.05), whereas it significantly increased activities of catalase in the hepatopancreas and glutathione-S-transferase in the hepatopancreas and intestine(P < 0.05).(Continued on next page)(Continued from previous page)Conclusions: The present results demonstrated that dietary methionine deficiency induced poor growth, and decreased digestive and absorptive function and antioxidant capacity in the hepatopancreas and intestine of sub-adult grass carp. Methionine requirements for sub-adult grass carp(450-1, 170 g) based on PWG, intestinal trypsin, and hepatopancreatic anti-hydroxyl radical activities were estimated to be 6.12 g/kg diet(21.80 g/kg protein),6.99 g/kg diet(24.90 g/kg protein) and 5.42 g/kg diet(19.31 g/kg protein), respectively, in the presence of 1.50 g cysteine/kg(5.35 g/kg protein).
基金Supported by the National Natural Science Foundation of China,No.39370780.
文摘AIM: To investigate the influence of L-methionine-deprived total parenteral nutrition with 5-FU on gastric cancer and host metabolism. METHODS: N-methyl-N'-nitro-nitrosoguanidine (MNNG) induced gastric cancer rats were randomly divided into four groups: Met-containing TPN group (n=11), Met-deprived TPN group (n =12), Met-containing TPN+5-FU group (n=11) and Met-deprived TPN+5-FU group (n=12). Five rats in each group were sacrificed after 7 days of treatment and the samples were taken for examination. The remaining rats in each group were then fed separately with normal diet after the treatment until death, the life span was noted. RESULTS: The tumors were enlarged in Met-containing group and shrank in Met-deprived group markedly after the treatment. The DNA index (DI) of tumor cells and the body weight (BW) of rats had no significant change in the two groups, however, the ratio of tumor cells'S phase was increased. The ratio of G2M phase went up in Met-containing group, but down in Met-deprived group. In the other two groups that 5-FU was added, the BW of rats, and the diameter of tumors, the DI of tumor cells, the S and G2M phase ratio of tumor cells were all decreased, particularly in Met-deprived plus 5-FU group. Pathological examination revealed that the necrotic foci of the tumor tissue increased after Met-deprived TPN treatment, and the nucleoli of tumor cells enlarged. In MetTPN+5-FU group, severe nuclear damage was also found by karyopyknosis and karyorrhexis, meanwhile there was slight degeneration in some liver and kidney cells. The serum free Met and Cysteine decreased markedly (P【0.001), while other amino acids, such as serum free serine and glutamine increased significantly (P【0.005). All the rats died of multiple organ failure caused by cancer metastasis. The average survival time was 18.6 days in Met-containing TPN group, 31 days in Met-deprived TPN group, 27.5 days in Met-containing TPN+5-FU group, and 43 days in Met-deprived TPN+5-FU group (P【0.05). CONCLUSION: Met-deprived TPN causes methionine starvation of tumor cells, and can enhance the anti-tumor effect of 5-FU and prolong the life span of gastric cancer bearing rats.
基金supported by the program for Changjiang Scholars and Innovative Research Team in University,China (IRT0848)the Education Department of Sichuan Province, China (09ZZ017)
文摘The purpose of this study was to investigate the effects of methionine deficiency on cellular immune function by determining morphological and ultrastructural changes of thymus, thymic cell cycle and apoptosis, peripheral blood T-cell subsets, T- cell proliferation function and the serum interleukin-2 （IL-2） contents. 120 1-d-old broilers were randomly divided into two groups （6 replicates in each group and l0 broilers in each replicate） and fed on a control diet or methionine deficient diet for 42 d. Lesions were observed in experiment. Histopathologically, lymphopenia and congestion were observed in the medulla of thymic lobule. Ultrastructurally, there were more apoptosis lymphocytes, and the mitochondria of lymphocytes were swelled in thymus of methionine deficiency. The G0/G~ phase of the cell cycle of the thymus was much higher （P〈0.01）, and the S, G2＋M phases and proliferating index （PI） were lower （P〈0.01） in methionine deficiency than in control group. And the percentage of apoptotic cells in the thymus was significantly increased in methionine deficiency （P〈0.01）. The percentage of CD4＋ and CD8~ T-cells was decreased in methionine deficiency compared with control group. Meanwhile, the proliferation function of peripheral blood T-cell was decreased in methionine deficiency. Also, the serum IL-2 contents were decreased in methionine deficiency. It was concluded that methionine deficiency could cause pathological and ultrastructural changes of thymus, reduce the T-cell population, serum IL-2 contents and the proliferation function of T- cells, and induce increased percentage of apoptotic cells. The cellular immune function was finally impaired in broilers.
