Mitochondrial malate dehydrogenase （mMDH） and citrate synthase （CS） are sequential enzymes in Krebs cycle. mMDH, CS and the complex between mMDH and CS （mMDH＋CS） were treated with nitric oxide solution. The rol...Mitochondrial malate dehydrogenase （mMDH） and citrate synthase （CS） are sequential enzymes in Krebs cycle. mMDH, CS and the complex between mMDH and CS （mMDH＋CS） were treated with nitric oxide solution. The roles of notric oxide （NO） on the secondary structures and the interactions between mMDH and CS were studied using circular diehroism （CD） and Fourier transform surface plasmon resonance （FT-SPR）, respectivley. The effects of NO on the activities of mMDH, CS and mMDH＋CS were also studied. And the regulations by NO on mMDH and CS were simulated by PyMOL software. The results of SPR conifrmed that strong interaction between mMDH and CS existed and NO could signiifcantly regulate the interaction between the two enzymes. NO reduced the mass percents ofα-helix and increased that of random in mMDH, CS and mMDH＋CS. NO increased the activities of CS and mMDH＋CS, and inhibited the activity of mMDH. Graphic simulation indicated that covalent bond was formed between NO and Asn242 in active site of CS. However, there was no direct bond between NO and mMDH. The increase in activity of mMDH＋CS complex depended mostly on the interaction between NO and CS. All the results suggested that the regulations by NO on the activity and interaction between mMDH and CS were accord with the changes in mMDH, CS and mMDH＋CS caused by NO.展开更多
Dear Editor,A hallmark of immune cells in response to inflammatory stimuli,both infectious and non-infectious,is the rapid and extensive change in metabolism.In addition to meet the energetic and biosynthetic need of ...Dear Editor,A hallmark of immune cells in response to inflammatory stimuli,both infectious and non-infectious,is the rapid and extensive change in metabolism.In addition to meet the energetic and biosynthetic need of the immune cell,research over the past decade has led to the appreciation of individual metabolites in cell signaling during metabolic reprogramming in immune response.One illustrative example is itaconate,a dicarboxylic acid derived from Kreb cycle metabolite,cis-aconitate,by the enzyme cis-aconitate decarboxylase(ACOD1).ACOD1 is encoded by immunoresponsive gene 1(IRG1),which is rapidly induced by various inflammatory stimuli in myeloid cells,leading to the prompt accumulation of itaconate to millimolar levels.Itaconate binds to multiple proteins to influence oxidative response,epigenetic modification,and gene expression intrinsically and to signal GPCR after secretion(Ye et al.,2024).These regulations on different pathways by a single metabolite concertedly modulate inflammatory responses.Beyond its role as an antimicrobial metabolite,itaconate has recently garnered attention in the research of cancer biology.Genetic and preclinical studies in animal models suggest that itaconate can create an immunosuppressive tumor microenvironment.The enhanced antitumor immunity and response to immune checkpoint inhibitors seen in Irg1-deficient mice,which otherwise exhibit normal development,underscore IRG1 as a compelling target for cancer immunotherapy(Chen et al.,2023;Gu et al.,2023;Zhao et al.,2022).However,current strategies to target IRG1/itaconate remain limited,emphasizing the need for therapeutic development to effectively blockade IRG1 in cancer treatment.展开更多
Objective：To investigate the effects of the ethyl acetate extract of Coreopsis tinctoria（EAEC）on insulin resistance（IR）in rats fed a high-fat diet.Methods：Male Sprague-Dawley（SD）rats were fed a HFD（60%fat）su...Objective：To investigate the effects of the ethyl acetate extract of Coreopsis tinctoria（EAEC）on insulin resistance（IR）in rats fed a high-fat diet.Methods：Male Sprague-Dawley（SD）rats were fed a HFD（60%fat）supplemented with EAEC for 8 weeks.The administration of EAEC to the rats with HFD-induced insulin resistance reduced hyperglycemia,plasma levels of insulin,and steatosis in the liver.Metabolomic study was used to analyze the metabolic levels of the high glucose-treated cells,control cells and marein-treated cells.Results：High glucose and high fat conditions caused a significant increase in blood glucose,insulin,serum TC,TG and LDL-C levels,leading to abnormal IR in rats.However,treatment with EAEC protects against HFD-induced IR by improving the fasting serum glucose homeostasis and lipid homeostasis.The high glucose conditions significantly decreased glycogen synthesis and increased PEPCK,G6Pase and Krebs cycle-related enzyme protein levels,leading to an abnormal metabolic state in Hep G2 cells.However,treatment with marein improved IR by increasing glucose uptake and glycogen synthesis and by downregulating PEPCK and G6Pase protein levels.The statistical analysis of the HPLC/MS data demonstrated that marein could restore the normal metabolic state.Conclusion：The results revealed that EAEC ameliorates IR in rats,and marein has the potential to improve IR by ameliorating glucose metabolism disorders.展开更多
基金supported by the National Natural Science Foundation of China (31270723, 31370686, 31470686)the Science and Technology Development Planning of Shandong Province, China (2013CEX20109)
文摘Mitochondrial malate dehydrogenase （mMDH） and citrate synthase （CS） are sequential enzymes in Krebs cycle. mMDH, CS and the complex between mMDH and CS （mMDH＋CS） were treated with nitric oxide solution. The roles of notric oxide （NO） on the secondary structures and the interactions between mMDH and CS were studied using circular diehroism （CD） and Fourier transform surface plasmon resonance （FT-SPR）, respectivley. The effects of NO on the activities of mMDH, CS and mMDH＋CS were also studied. And the regulations by NO on mMDH and CS were simulated by PyMOL software. The results of SPR conifrmed that strong interaction between mMDH and CS existed and NO could signiifcantly regulate the interaction between the two enzymes. NO reduced the mass percents ofα-helix and increased that of random in mMDH, CS and mMDH＋CS. NO increased the activities of CS and mMDH＋CS, and inhibited the activity of mMDH. Graphic simulation indicated that covalent bond was formed between NO and Asn242 in active site of CS. However, there was no direct bond between NO and mMDH. The increase in activity of mMDH＋CS complex depended mostly on the interaction between NO and CS. All the results suggested that the regulations by NO on the activity and interaction between mMDH and CS were accord with the changes in mMDH, CS and mMDH＋CS caused by NO.
基金supported by grants from Noncommunicable Chronic Diseases-National Science and Technology Major Program(No.2023ZD0500400 to D.Y.and Y.L.)the National Key R&D Program of China(No.2020YFA 0803202 to D.Y.and No.2019YFA 0802900 to Y.L.)+2 种基金the Fundamental Research Funds for the Central Universities(No.2024300408 to Y.L.)the Jiangsu Provincial Science and Technology Plan Special Fund(No.BK20232018 to Y.L.)NSFC grants(Nos.82225036,31821002,and 31871431 to D.Y.,Nos.82103366 and 32370823 to L-L.C.,Nos.32122035 and 32471000 to Y.L.)。
文摘Dear Editor,A hallmark of immune cells in response to inflammatory stimuli,both infectious and non-infectious,is the rapid and extensive change in metabolism.In addition to meet the energetic and biosynthetic need of the immune cell,research over the past decade has led to the appreciation of individual metabolites in cell signaling during metabolic reprogramming in immune response.One illustrative example is itaconate,a dicarboxylic acid derived from Kreb cycle metabolite,cis-aconitate,by the enzyme cis-aconitate decarboxylase(ACOD1).ACOD1 is encoded by immunoresponsive gene 1(IRG1),which is rapidly induced by various inflammatory stimuli in myeloid cells,leading to the prompt accumulation of itaconate to millimolar levels.Itaconate binds to multiple proteins to influence oxidative response,epigenetic modification,and gene expression intrinsically and to signal GPCR after secretion(Ye et al.,2024).These regulations on different pathways by a single metabolite concertedly modulate inflammatory responses.Beyond its role as an antimicrobial metabolite,itaconate has recently garnered attention in the research of cancer biology.Genetic and preclinical studies in animal models suggest that itaconate can create an immunosuppressive tumor microenvironment.The enhanced antitumor immunity and response to immune checkpoint inhibitors seen in Irg1-deficient mice,which otherwise exhibit normal development,underscore IRG1 as a compelling target for cancer immunotherapy(Chen et al.,2023;Gu et al.,2023;Zhao et al.,2022).However,current strategies to target IRG1/itaconate remain limited,emphasizing the need for therapeutic development to effectively blockade IRG1 in cancer treatment.
基金supported by funding from the National Natural Science Foundation of China(grant 81573576,81703223)the China Postdoctoral Science Foundation(2017M611127)
文摘Objective：To investigate the effects of the ethyl acetate extract of Coreopsis tinctoria（EAEC）on insulin resistance（IR）in rats fed a high-fat diet.Methods：Male Sprague-Dawley（SD）rats were fed a HFD（60%fat）supplemented with EAEC for 8 weeks.The administration of EAEC to the rats with HFD-induced insulin resistance reduced hyperglycemia,plasma levels of insulin,and steatosis in the liver.Metabolomic study was used to analyze the metabolic levels of the high glucose-treated cells,control cells and marein-treated cells.Results：High glucose and high fat conditions caused a significant increase in blood glucose,insulin,serum TC,TG and LDL-C levels,leading to abnormal IR in rats.However,treatment with EAEC protects against HFD-induced IR by improving the fasting serum glucose homeostasis and lipid homeostasis.The high glucose conditions significantly decreased glycogen synthesis and increased PEPCK,G6Pase and Krebs cycle-related enzyme protein levels,leading to an abnormal metabolic state in Hep G2 cells.However,treatment with marein improved IR by increasing glucose uptake and glycogen synthesis and by downregulating PEPCK and G6Pase protein levels.The statistical analysis of the HPLC/MS data demonstrated that marein could restore the normal metabolic state.Conclusion：The results revealed that EAEC ameliorates IR in rats,and marein has the potential to improve IR by ameliorating glucose metabolism disorders.
