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Reversible inactivation of dihydrolipoamide dehydrogenase by Angeli's salt. 安吉利盐对二氢脂酰胺脱氢酶的可逆灭活作用。

生物物理学报 Pub Date : 2012-04-20

Liang-Jun Yan, Li Liu, Michael J Forster

{"title":"Reversible inactivation of dihydrolipoamide dehydrogenase by Angeli's salt.","authors":"Liang-Jun Yan, Li Liu, Michael J Forster","doi":"","DOIUrl":"","url":null,"abstract":"Dihydrolipoamide dehydrogenase (DLDH) is a key component of 3 mitochondrial α-keto acid dehydrogenase complexes including pyruvate dehydrogenase complex, α-ketoglutarate dehydrogenase complex, and branched chain amino acid dehydrogenase complex. It is a pyridine-dependent disulfide oxidoreductase that is very sensitive to oxidative modifications by reactive nitrogen species (RNS) and reactive oxygen species (ROS). The objective of this study was to investigate the mechanisms of DLDH modification by RNS derived from Angeli's salt. Studies were conducted using isolated rat brain mitochondria that were incubated with varying concentrations of Angeli's salt followed by spectrophotometric enzyme assays, blue native gel analysis, and 2-dimensional gel-based proteomic approaches. Results show that DLDH could be inactivated by Angeli's salt in a concentration dependent manner and the inactivation was a targeting rather than a random process as peroxynitrite did not show any detectable inhibitory effect on the enzyme's activity under the same experimental conditions. Since Angeli's salt can readily decompose at physiological pH to yield nitroxyl anion (HNO) and nitric oxide, further studies were conducted to determine the actual RNS that was responsible for DLDH inactivation. Results indicate that it was HNO that exerted the effect of Angeli's salt on DLDH. Finally, two-dimensional Western blot analysis indicates that DLDH inactivation by Angeli's salt was accompanied by formation of protein s-nitrosothiols, suggesting that s-nitrosylation is likely the cause of loss in enzyme's activity. Taken together, the present study provides insights into mechanisms of DLDH inactivation induced by HNO derived from Angeli's salt.","PeriodicalId":62275,"journal":{"name":"生物物理学报","volume":"28 4","pages":"341-350"},"PeriodicalIF":0.0,"publicationDate":"2012-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490496/pdf/nihms383847.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31038121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of SREBP-Mediated Gene Expression. srebp介导的基因表达调控。

生物物理学报 Pub Date : 2012-01-01 DOI: 10.3724/SP.J.1260.2012.20034

Zhao Xiaoping, Yang Fajun

{"title":"Regulation of SREBP-Mediated Gene Expression.","authors":"Zhao Xiaoping, Yang Fajun","doi":"10.3724/SP.J.1260.2012.20034","DOIUrl":"https://doi.org/10.3724/SP.J.1260.2012.20034","url":null,"abstract":"The sterol regulatory element-binding proteins (SREBPs) play an important role in regulating lipid homeostasis. Translated as inactive precursors that are localized in the endoplasmic reticulum (ER) membrane, SREBPs are activated through a proteolytic process in response to intracellular demands for lipids. The cleaved amino-terminal fragments of SREBPs then translocate into the nucleus as homodimers and stimulate the transcription of target genes by binding to the sterol response elements (SREs) in their promoters. Numerous studies using cell culture or genetically modified mouse models have demonstrated that the major target genes of SREBPs include rate-limiting enzymes in the pathways of fatty acid and cholesterol biosynthesis as well as the low-density lipoprotein (LDL) receptor. The proteolytic maturation of SREBPs has been well studied in the past. However, recent studies have also improved our understanding on the regulation of nuclear SREBPs. In the nucleus, SREBPs interact with specific transcriptional cofactors, such as CBP/p300 and the Mediator complex, resulting in stimulation or inhibition of their transcriptional activities. In addition, nuclear SREBP protein stability is dynamically regulated by phosphorylation and acetylation. Such protein-protein interactions and post-translational modifications elegantly link the extracellular signals, such as insulin, or intracellular signals, such as oxidative stress, to lipid biosynthesis by modulating the transcriptional activity of SREBPs. Under normal physiological states, lipid homeostasis is strictly maintained. However, the SREBP pathways are often dysregulated in pathophysiological conditions, such as obesity, type 2 diabetes, and fatty liver diseases. Thus, the novel regulatory mechanisms of SREBPs may provide new opportunities for fighting these metabolic diseases.","PeriodicalId":62275,"journal":{"name":"生物物理学报","volume":"28 4","pages":"287-294"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3724/SP.J.1260.2012.20034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31475076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19