Search results for: succinateCoA
#39411885 2024/10/16 To Up
Ketogenic β-hydroxybutyrate regulates β-hydroxybutyrylation of TCA cycle-associated enzymes and attenuates disease-associated pathologies in Alzheimer's mice.
Lysine β-hydroxybutyrylation (Kbhb) is a post-translational modification that has recently been found to regulate protein functions. However, whether and how protein Kbhb modification participates in Alzheimer's disease (AD) remains unknown. Herein, we carried out 4D label-free β-hydroxybutylation quantitative proteomics using brain samples of 8-month-old and 2-month-old APP/PS1 AD model mice and wild-type (WT) controls. We identified a series of tricarboxylic acid (TCA) cycle-associated enzymes including citrate synthase (CS) and succinate-CoA ligase subunit alpha (SUCLG1), whose Kbhb modifications were decreased in APP/PS1 mice at pathological stages. Sodium β-hydroxybutyrate (Na-β-OHB) treatment markedly increased Kbhb modifications of CS and SUCLG1 and their enzymatic activities, leading to elevated ATP production. We further found that Kbhb modifications at lysine 393 site in CS and at lysine 81 site in SUCLG1 were crucial for their enzymatic activities. Finally, we found that β-OHB levels were decreased in the brain of APP/PS1 mice at pathological stages. While ketogenic diet not only significantly increased β-OHB levels, Kbhb modifications and enzymatic activities of CS and SUCLG1, and ATP production, but also dramatically attenuated β-amyloid plaque pathologies and microgliosis in APP/PS1 mice. Together, our findings indicate the importance of protein Kbhb modification for maintaining normal TCA cycle and ATP production and provide a novel molecular mechanism underlying the beneficial effects of ketogenic diet on energy metabolism and AD intervention.Wanhong Han, Bingchang Zhang, Wenpeng Zhao, Wentao Zhao, Jiawei He, Xiansheng Qiu, Liang Zhang, Xiuyan Wang, Yong Wang, Hanwen Lu, Yaya Zhang, Yuanyuan Xie, Yanyan Geng, Wujie Zhao, Qionghui Huang, Yun-Wu Zhang, Zhanxiang Wang
1643 related Products with: Ketogenic β-hydroxybutyrate regulates β-hydroxybutyrylation of TCA cycle-associated enzymes and attenuates disease-associated pathologies in Alzheimer's mice.
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#39070054 2024/07/11 To Up
Two novel variants cause mitochondrial DNA depletion syndrome, type 5 in two siblings.
Mitochondrial DNA depletion syndrome (MDS), characterized by succinate-CoA ligase deficiency and loss of mitochondrial DNA (mtDNA), is caused by specific variants in nuclear genes responsible for mtDNA maintenance. -related mitochondrial DNA depletion syndrome, type 5 (MTDPS-5), presents as a rare, severe early progressive encephalomyopathy. This report investigates a new family exhibiting clinical manifestations of MTDPS-5 and elucidates the genetic basis of this disorder. In two affected siblings, a novel maternally inherited nonsense variant [c.1234C>T (p.Arg412*)] in the gene and a unique paternally inherited indel variant (g.48569263-48571020del1758insATGA) were identified. Additionally, the siblings exhibited blood mtDNA content lower than 33% compared to age-matched controls. These findings underscore the importance of assessing variants in patients with severe early progressive encephalomyopathy, even in the absence of methylmalonic aciduria or mtDNA loss, thereby broaden the mutational spectrum of this gene.Xiaohuan Zhang, Guo Zhang, Li Cao, Wenjing Zhou, Chang Tan, Shi Ma, Jiyun Yang
2894 related Products with: Two novel variants cause mitochondrial DNA depletion syndrome, type 5 in two siblings.
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#39036799 2024/06/13 To Up
Nitrite-driven anaerobic ethane oxidation.
Ethane, the second most abundant gaseous hydrocarbon in vast anoxic environments, is an overlooked greenhouse gas. Microbial anaerobic oxidation of ethane can be driven by available electron acceptors such as sulfate and nitrate. However, despite nitrite being a more thermodynamically feasible electron acceptor than sulfate or nitrate, little is known about nitrite-driven anaerobic ethane oxidation. In this study, a microbial culture capable of nitrite-driven anaerobic ethane oxidation was enriched through the long-term operation of a nitrite-and-ethane-fed bioreactor. During continuous operation, the nitrite removal rate and the theoretical ethane oxidation rate remained stable at approximately 25.0 mg NO N L d and 11.48 mg CH L d, respectively. Batch tests demonstrated that ethane is essential for nitrite removal in this microbial culture. Metabolic function analysis revealed that a species affiliated with a novel genus within the family Rhodocyclaceae, designated as ' Alkanivoras nitrosoreducens', may perform the nitrite-driven anaerobic ethane oxidation. In the proposed metabolic model, despite the absence of known genes for ethane conversion to ethyl-succinate and succinate-CoA ligase, '. A. nitrosoreducens' encodes a prospective fumarate addition pathway for anaerobic ethane oxidation and a complete denitrification pathway for nitrite reduction to nitrogen. These findings advance our understanding of nitrite-driven anaerobic ethane oxidation, highlighting the previously overlooked impact of anaerobic ethane oxidation in natural ecosystems.Cheng-Cheng Dang, Yin-Zhu Jin, Xin Tan, Wen-Bo Nie, Yang Lu, Bing-Feng Liu, De-Feng Xing, Nan-Qi Ren, Guo-Jun Xie
2218 related Products with: Nitrite-driven anaerobic ethane oxidation.
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#38772315 2024/05/16 To Up
The tricarboxylic acid cycle is inhibited under acute stress from carbonate alkalinity in the gills of Eriocheir sinensis.
Owing to population growth and environmental pollution, freshwater aquaculture has been rapidly shrinking in recent years. Aquaculture in saline-alkaline waters is a crucial strategy to meet the increasing demand for aquatic products. The Chinese mitten crab is an important economic food in China, but the molecular mechanism by which it tolerates carbonate alkalinity (CA) in water remains unclear. Here, we found that enzyme activities of the tricarboxylic acid (TCA) cycle in the gills, such as citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase, were markedly reduced under CA stress induced by 40 mM NaHCO. Secondly, the TCA cycle in the gills is inhibited under acute CA stress, according to proteomic and metabolomic analyses. The expressions of six enzymes, namely aconitate hydratase, isocitrate dehydrogenase, 2-oxoglutarate dehydrogenase, dihydrolipoyl dehydrogenase, succinate-CoA ligase, and malate dehydrogenase, were downregulated, resulting in the accumulation of phosphoenolpyruvic acid, citric acid, cis-aconitate, and α-ketoglutaric acid. Finally, we testified that if the TCA cycle is disturbed by malonate, the survival rate increases in CA water. To our knowledge, this is the first study to show that the TCA cycle in the gills is inhibited under CA stress. Overall, the results provide new insights into the molecular mechanism of tolerance to saline-alkaline water in crabs, which helped us expand the area for freshwater aquaculture and comprehensively understand the physiological characteristics of crab migration.Chao Wang, Li An, Xue-Sa Dong, Xiao Xu, Xiu-Yun Feng, Zhi-Zhong Wang, Fei He, Xi Chen, Yong-An Zhu, Qing-Lei Meng
1784 related Products with: The tricarboxylic acid cycle is inhibited under acute stress from carbonate alkalinity in the gills of Eriocheir sinensis.
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#38657916 2024/04/22 To Up
Identification of the succinate-CoA ligase protein gene family reveals that TaSUCL1-1 positively regulate cadmium resistance in wheat.
The Succinate-CoA ligase (SUCL1) gene family is involved in energy metabolism, phytohormone signaling, and plant growth, development, and tolerance to stress. This is the first study to analyze the SUCL1 gene family in wheat (Triticum aestivum). 17 TaSUCL1 genes were identified in the complete genome sequence and classified into five subfamilies based on related genes found in three other species. The 17 TaSUCL1 genes were unevenly distributed across 11 chromosomes, and the collinearity of these genes was further investigated. Through using real-time qPCR (RT-qPCR) analysis, we identified the expression patterns of the TaSUCL1 genes under various tissues and different heavy metal stress conditions. The functions of selected TaSUCL1-1 gene were investigated by RNA interference (RNAi). This study provided a comprehensive analysis of the TaSUCL1 gene family. Within the TaSUCL1 genes, the exon-intron structure and motif composition exhibited significant similarity among members of the same evolutionary branch. Homology analysis and phylogenetic comparison of the SUCL1 genes in different plants offered valuable insights for studying the evolutionary characteristics of the SUCL1 genes. The expression levels of the TaSUCL1 genes in different tissues and under various metal stress conditions reveal its important role in plant growth and development. Gene function analysis demonstrated that TaSUCL1-1 silenced wheat plants exhibited a decrease in the total cadmium (Cd) concentrations and gene expression levels compared to the wild type (WT). Additionally, TaSUCL1-1 belonging to class c physically interacts with the β-amylase protein TaBMY1 as verified by yeast two-hybridization. This research provides a useful resource for further study of the function and molecular genetic mechanism of the SUCL1 gene family members.Liuliu Wu, Lifan Cao, Ye Tao, Halyna Zhatova, Haiyan Hu, Chengwei Li
2265 related Products with: Identification of the succinate-CoA ligase protein gene family reveals that TaSUCL1-1 positively regulate cadmium resistance in wheat.
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#38649537 2024/04/22 To Up
SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression.
Mitochondria are cellular powerhouses that generate energy through the electron transport chain (ETC). The mitochondrial genome (mtDNA) encodes essential ETC proteins in a compartmentalized manner, however, the mechanism underlying metabolic regulation of mtDNA function remains unknown. Here, we report that expression of tricarboxylic acid cycle enzyme succinate-CoA ligase SUCLG1 strongly correlates with ETC genes across various TCGA cancer transcriptomes. Mechanistically, SUCLG1 restricts succinyl-CoA levels to suppress the succinylation of mitochondrial RNA polymerase (POLRMT). Lysine 622 succinylation disrupts the interaction of POLRMT with mtDNA and mitochondrial transcription factors. SUCLG1-mediated POLRMT hyposuccinylation maintains mtDNA transcription, mitochondrial biogenesis, and leukemia cell proliferation. Specifically, leukemia-promoting FMS-like tyrosine kinase 3 (FLT3) mutations modulate nuclear transcription and upregulate SUCLG1 expression to reduce succinyl-CoA and POLRMT succinylation, resulting in enhanced mitobiogenesis. In line, genetic depletion of POLRMT or SUCLG1 significantly delays disease progression in mouse and humanized leukemia models. Importantly, succinyl-CoA level and POLRMT succinylation are downregulated in FLT3-mutated clinical leukemia samples, linking enhanced mitobiogenesis to cancer progression. Together, SUCLG1 connects succinyl-CoA with POLRMT succinylation to modulate mitochondrial function and cancer development.Weiwei Yan, Chengmei Xie, Sijun Sun, Quan Zheng, Jingyi Wang, Zihao Wang, Cheuk-Him Man, Haiyan Wang, Yunfan Yang, Tianshi Wang, Leilei Shi, Shengjie Zhang, Chen Huang, Shuangnian Xu, Yi-Ping Wang
2596 related Products with: SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression.
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#37838251 2023/10/13 To Up
Quantitative proteomics reveals the neurotoxicity of trimethyltin chloride on mitochondria in the hippocampus of mice.
Trimethyltin chloride (TMT) is a potent neurotoxin widely used as a constituent of polyvinyl chloride plastic in the industrial and agricultural fields. However, the underlying mechanisms by which TMT leads to neurotoxicity remain elusive. In the present study, we constructed a dose and time dependent neurotoxic mouse model of TMT exposure to explore the molecular mechanisms involved in TMT-induced neurological damage. Based on this model, the cognitive ability of TMT exposed mice was assessed by the Morris water maze test and a passive avoidance task. The ultrastructure of hippocampus was analyzed by the transmission electron microscope. Subsequently, proteomics integrated with bioinformatics and experimental verification were employed to reveal potential mechanisms of TMT-induced neurotoxicity. Gene ontology (GO) and pathway enrichment analysis were done by using Metascape and GeneCards database respectively. Our results demonstrated that TMT-exposed mice exhibited cognitive disorder, and mitochondrial respiratory chain abnormality of the hippocampus. Proteomics data showed that a total of 7303 proteins were identified in hippocampus of mice of which 224 ones displayed a 1.5-fold increase or decrease in TMT exposed mice compared with controls. Further analysis indicated that these proteins were mainly involved in tricarboxylic acid (TCA) cycle and respiratory electron transport, proteasome degradation, and multiple metabolic pathways as well as inflammatory signaling pathways. Some proteins, including succinate-CoA ligase subunit (Suclg1), NADH dehydrogenase subunit 5 (Nd5), NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 (Ndufa4l2) and cytochrome c oxidase assembly factor 7 (Coa7), which were closely related to mitochondrial respiratory electron transport, showed TMT dose and time dependent changes in the hippocampus of mice. Moreover, apoptotic molecules Bax and cleaved caspase-3 were up-regulated, while anti-apoptotic Bcl-2 was down-regulated compared with controls. In conclusion, our findings suggest that impairment of mitochondrial respiratory chain transport and promotion of apoptosis are the potential mechanisms of TMT induced hippocampus toxicity in mice.Zhenzhong Liu, Li Wang, Yue Wang, Siya Wu, Caiting Peng, Yu Wang, Ming Huang, Li Che, Rongjing Sun, Xi Zhao, Zuo Du, Wenhu Liu
1428 related Products with: Quantitative proteomics reveals the neurotoxicity of trimethyltin chloride on mitochondria in the hippocampus of mice.
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#37298114 2023/05/23 To Up
Carbonic Anhydrase Regulates Cytoplasmic pH of Nitrogen-Fixing Vesicles.
A phyloprofile of genomes was carried out to identify those genes present in symbiotic strains of clusters 1, 1c, 2 and 3 and absent in non-infective strains of cluster 4. At a threshold of 50% AA identity, 108 genes were retrieved. Among these were known symbiosis-associated genes such as (nitrogenase), and genes which are not know as symbiosis-associated genes such as (carbonic anhydrase, CAN). The role of CAN, which supplies carbonate ions necessary for carboxylases and acidifies the cytoplasm, was thus analyzed by staining cells with pH-responsive dyes; assaying for CO levels in N-fixing propionate-fed cells (that require a propionate-CoA carboxylase to yield succinate-CoA), fumarate-fed cells and N-replete propionate-fed cells; conducting proteomics on N-fixing fumarate and propionate-fed cells and direct measurement of organic acids in nodules and in roots. The interiors of both in vitro and nodular vesicles were found to be at a lower pH than that of hyphae. CO levels in N-fixing propionate-fed cultures were lower than in N-replete ones. Proteomics of propionate-fed cells showed carbamoyl-phosphate synthase (CPS) as the most overabundant enzyme relative to fumarate-fed cells. CPS combines carbonate and ammonium in the first step of the citrulline pathway, something which would help manage acidity and NH. Nodules were found to have sizeable amounts of pyruvate and acetate in addition to TCA intermediates. This points to CAN reducing the vesicles' pH to prevent the escape of NH and to control ammonium assimilation by GS and GOGAT, two enzymes that work in different ways in vesicles and hyphae. Genes with related functions (carboxylases, biotin operon and citrulline-aspartate ligase) appear to have undergone decay in non-symbiotic lineages.Petar Pujic, Lorena Carro, Pascale Fournier, Jean Armengaud, Guylaine Miotello, Nathalie Dumont, Caroline Bourgeois, Xavier Saupin, Patrick Jame, Gabriela Vuletin Selak, Nicole Alloisio, Philippe Normand
2070 related Products with: Carbonic Anhydrase Regulates Cytoplasmic pH of Nitrogen-Fixing Vesicles.
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#37216870 2023/05/20 To Up
Metabolic enzyme Suclg2 maintains tolerogenicity of regulatory dendritic cells diffDCs by suppressing Lactb succinylation.
Metabolic reprogramming plays a pivotal role in the differentiation and function of immune cells including dendritic cells (DCs). Regulatory DCs can be generated in regional tissue niches like splenic stroma and act as an important part of stromal control of immune response for the maintenance of immune tolerance. However, the metabolic alterations during splenic stroma-driven regulatory DCs differentiation and the metabolic enzyme involved in regulatory DCs function remain poorly understood. By combining metabolomic, transcriptomic, and functional investigations of mature DCs (maDCs) and diffDCs (regulatory DCs differentiated from activated mature DCs through coculturing with splenic stroma), here we identified succinate-CoA ligase subunit beta Suclg2 as a key metabolic enzyme that reprograms the proinflammatory status of mature DCs into a tolerogenic phenotype via preventing NF-κB signaling activation. diffDCs downregulate succinic acid levels and increase the Suclg2 expression along with their differentiation from mature DCs. Suclg2-interference impaired the tolerogenic function of diffDCs in inducing T cell apoptosis and enhanced activation of NF-κB signaling and expression of inflammatory genes CD40, Ccl5, and Il12b in diffDCs. Furthermore, we identified Lactb as a new positive regulator of NF-κB signaling in diffDCs whose succinylation at the lysine 288 residue was inhibited by Suclg2. Our study reveals that the metabolic enzyme Suclg2 is required to maintain the immunoregulatory function of diffDCs, adding mechanistic insights into the metabolic regulation of DC-based immunity and tolerance.Xiaomin Zhang, Juan Liu, Yujie Cheng, Kun Chen, Yali Chen, Ha Zhu, Zhiqing Li, Shuxun Liu, Xuetao Cao
2624 related Products with: Metabolic enzyme Suclg2 maintains tolerogenicity of regulatory dendritic cells diffDCs by suppressing Lactb succinylation.
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#36697366 2023/01/25 To Up
Genome-wide association studies demonstrate the genes associated with perimysial thickness in ducks.
The thickness of the perimysium has an essential effect on the tenderness of the meat. However, the genetic basis underlying perimysial thickness has not been determined. The objective of this study was to explore the quantitative trait loci (QTL) that influence perimysial thickness in an F segregating population generated by Mallard × Pekin duck using the genome-wide association study (GWAS) method. Two QTL identified in chromosomes 27 and 13 displayed significant associations with perimysial thickness traits at the genome-wide level. The strongest association was the QTL located in chromosome 27, and this region had an effect on perimysial thickness and contained a promising candidate gene MAGI3 (Membrane-associated guanylate kinase, WW and PDZ domain containing 3). Meanwhile, association analysis showed that the top SNP within the MAGI3 gene was also associated with intramuscular fat content traits, which showed that perimysial thickness was positively correlated with intramuscular fat content. The second strongest association was the QTL region of chromosome 13. SUCLG2 (Succinate-CoA ligase GDP-forming subunit beta) is proximal to the top SNP and stood out as another candidate gene. Furthermore, the Transposase-Accessible Chromatin using Sequencing result showed that some key transcription factors (MYF5, MYOD1, KLF11) related to muscle development or energy metabolism might bind to the open regions of MAGI3 and SUCLG2. By analyzing the expression of different genotypes of the candidate gene, we speculate that different genotypes of MAGI3 may have an effect on breast muscle development, and then affect the thickness of the perimysium. This study maps two major genes of the duck breast muscle perimysial thickness trait, which helps to characterize muscle development and contributes to the genetic improvement of meat yield and quality in livestock.Hehe Tang, Dapeng Liu, Huiling Zhang, Wenlei Fan, Jian Hu, Yaxi Xu, Zhanbao Guo, Wei Huang, Shuisheng Hou, Zhengkui Zhou
1732 related Products with: Genome-wide association studies demonstrate the genes associated with perimysial thickness in ducks.
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