AI Article Synopsis
Article Abstract
The alpha-ketoglutarate dehydrogenase complex (KGDHC) is a mitochondrial enzyme in the TCA cycle. Inhibition of KGDHC activity by alpha-keto-beta-methyl-n-valeric acid (KMV) is associated with neuron death. However, the effect of KMV in microglia is unclear. Therefore, we investigated the effect of KMV on BV-2 microglial cells exposed to hypoxia or oxidative stress. The results showed that KMV (1-20 mM) enhanced the cell viability under hypoxia. KMV dose-dependently reduced ROS and LDH releases from hypoxic BV-2 cells. KMV also reduced ROS production and enhanced the cell viability under H2O2 but failed to reduce the SIN-1 and sodium nitroprusside (SNP) toxicity. KMV also reduced caspase-3 and -9 activation under stress. These results suggest that KMV protects BV-2 cells from stress and acts by reducing ROS production through inhibition of KDGHC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1196/annals.1338.049 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
α-Ketoisocaproic Acid Disrupts Mitochondrial Bioenergetics in the Brain of Neonate Rats: Molecular Modeling Studies of α-ketoglutarate Dehydrogenase Subunits Inhibition.
Neurochem Res
January 2025
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Brain accumulation of the branched-chain α-keto acids α-ketoisocaproic acid (KIC), α-keto-β-methylvaleric acid (KMV), and α-ketoisovaleric acid (KIV) occurs in maple syrup urine disease (MSUD), an inherited intoxicating metabolic disorder caused by defects of the branched-chain α-keto acid dehydrogenase complex. Patients commonly suffer life-threatening acute encephalopathy in the newborn period and develop chronic neurological sequelae of still undefined pathogenesis. Therefore, this work investigated the in vitro influence of pathological concentrations of KIC (5 mM), KMV (1 mM), and KIV (1 mM) on mitochondrial bioenergetics in the cerebral cortex of neonate (one-day-old) rats.
View Article and Find Full Text PDFLC-MS/MS method for quantitative profiling of ketone bodies, α-keto acids, lactate, pyruvate and their stable isotopically labelled tracers in human plasma: An analytical panel for clinical metabolic kinetics and interactions.
J Chromatogr B Analyt Technol Biomed Life Sci
November 2023
Clinical Metabolomics Core Facility (CMCF), Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:
An important area within clinical research is in vivo metabolism of ketone bodies (β-hydroxybutyrate and acetoacetate) and in connection metabolites that may affect their production and/or cellular transport such as the keto-acids from the branched-chain amino acids, lactate and pyruvate. To determine in vivo metabolite turnover, availability of accurate and sensitive methods for analyzing the plasma concentrations of these metabolites and their stable isotopically labeled enrichments is mandatory. Therefore, the present study describes a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous analysis of ketone bodies, α-keto acids, lactate, pyruvate, and their tracer enrichments in humans using 2 different derivatization techniques with 4-bromo-N-methylbenzylamine and O-benzylhydroxylamine as derivatization reagents, and 1-ethyl-3-dimethylaminopropyl carbodiimide as coupling compound followed by a single LC-MS/MS run.
View Article and Find Full Text PDFAcute effects of intracerebroventricular administration of α-ketoisocaproic acid in young rats on inflammatory parameters.
Metab Brain Dis
June 2023
Laboratório de Doenças Neurometabólicas, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, Brazil.
Maple Syrup Urine Disease (MSUD) is an autosomal recessive inborn error of metabolism (IEM), responsible for the accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, in addition to their α-keto acids α-ketoisocaproic acid (KIC), α-keto-β-methylvaleric acid (KMV), and α-ketoisovaleric acid (KIV) in the plasma and urine of patients. This process occurs due to a partial or total blockage of the dehydrogenase enzyme activity of branched-chain α-keto acids. Oxidative stress and inflammation are conditions commonly observed on IEM, and the inflammatory response may play an essential role in the pathophysiology of MSUD.
View Article and Find Full Text PDFThe glutathionylation agent disulfiram augments superoxide/hydrogen peroxide production when liver mitochondria are oxidizing ubiquinone pool-linked and branched chain amino acid substrates.
Free Radic Biol Med
August 2021
The School of Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Ste.-Anne-de-Bellevue, Quebec, Canada. Electronic address:
Our group has previously observed that protein S-glutathionylation serves as an integral feedback inhibitor for the production of superoxide (O)/hydrogen peroxide (HO) by α-ketoglutarate dehydrogenase (KGDH), pyruvate dehydrogenase (PDH), and complex I in muscle and liver mitochondria, respectively. In the present study, we hypothesized that glutathionylation would fulfill a similar role for the O/HO sources sn-glycerol-3-phosphate dehydrogenase (G3PDH), proline dehydrogenase (PRODH), and branched chain keto acid dehydrogenase (BCKDH). Surprisingly, we found that inducing glutathionylation with disulfiram increased the production of O/HO by mitochondria oxidizing glycerol-3-phosphate (G3P), proline (Pro), or α-keto-β-methylvaleric acid (KMV).
View Article and Find Full Text PDFFast analysis using pillar array columns: Quantification of branched-chain α-keto acids in human plasma samples.
J Pharm Biomed Anal
May 2021
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 1130033, Japan. Electronic address:
Branched-chain α-keto acids (BCKAs, namely, α-ketoisovaleric acid (KIV), α-ketoisocaproic acid (KIC), and α-keto-β-methylvaleric acid (KMV)) are related to many diseases such as myeloid leukemia, liver cancer, and diabetes mellitus. A rapid quantitative analytical method for BCKAs using pillar array columns was developed. α-Keto acids were labeled with 1,2-diamino-4,5-methylenedioxybenzene (DMB), followed by their separation on octadecylsilane-treated pillar array columns with MeOH/HO as the mobile phase.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!