Novel functions of the alpha-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease.

Novel functions of the alpha-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Novel functions of the alpha-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease. Abstract Text:

Qingli Shi,Hui Xu,Wayne A Kleinman,Gary E Gibson,

Measures in autopsied brains from Alzheimer's Disease (AD) patients reveal a decrease in the activity of alpha-ketoglutarate dehydrogenase complex (KGDHC) and an increase in malate dehydrogenase (MDH) activity. The present experiments tested whether both changes could be caused by the common oxidant H(2)O(2) and to probe the mechanism underlying these changes. Since the response to H(2)O(2) is modified by the level of the E2k subunit of KGDHC, the interaction of MDH and KGDHC was studied in cells with varying levels of E2k. In cells with only 23% of normal E2k protein levels, one-hour treatment with H(2)O(2) decreased KGDHC and increased MDH activity as well as the mRNA level for both cytosolic and mitochondrial MDH. The increase in MDH did not occur in cells with 100% or 46% of normal E2k. Longer treatments with H(2)O(2) inhibited the activity of both enzymes. Glutathione is a major regulator of cellular redox state and can modify enzyme activities. H(2)O(2) converts reduced glutathione (GSH) to oxidized glutathione (GSSG), which reacts with protein thiols. Treatment of purified KGDHC with GSSG leads to glutathionylation of all three KGDHC subunits. Thus, cellular glutathione level was manipulated by two means to determine the effect on KGDHC and MDH activities. Both buthionine sulfoximine (BSO), which inhibits glutathione synthesis without altering redox state, and H(2)O(2) diminished glutathione to a similar level after 24 h. However, H(2)O(2), but not BSO, reduced KGDHC and MDH activities, and the reduction was greater in the E2k-23 line. These findings suggest that the E2k may mediate diverse responses of KGDHC and MDH to oxidants. In addition, the differential response of activities to BSO and H(2)O(2) together with the in vitro interaction of KGDHC with GSSG suggests that glutathionylation is one possible mechanism underlying oxidative stress-induced inhibition of the TCA cycle enzymes.

Novel functions of the alpha-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease. Publishing Authors By Initials

Q Shi,H Xu,WA Kleinman,GE Gibson,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Novel functions of the alpha-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biochimica et biophysica acta

VOLUME: 1782

Page Numbers: 229-38

Journal Abbreviation: Biochim. Biophys. Acta

ISSN: 0006-3002

DAY: 31

MONTH: 12

YEAR: 2007

Novel functions of the alpha-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 217513

Novel functions of the alpha-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Novel functions of the alpha-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Novel functions of the alpha-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease.

AFFILIATION: Department of Neurology and Neuroscience, Weill Medical College of Cornell University/Burke Medical Research Institute, 785 Mamaroneck Ave., White Plains, New York 10605, USA.

Country: Netherlands

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Biochim Biophys Acta

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Novel functions of the alpha-ketoglutarate dehydrogenase complex may mediate diverse oxidant-induced changes in mitochondrial enzymes associated with Alzheimer's disease Related Publications

• A key to understanding trypanosoma trees.
• A supramolecular poly[3]pseudorotaxane by self-assembly of a homoditopic cylindrical bis(crown ether) host and a bisparaquat derivative.
• Adjusted 200-day scrotal size as a predictor of 365-day scrotal circumference.
• An optical signal correlated with the allosteric transition in Scapharca inaequivalvis HbI.
• Asthma action plans: use it or lose it.
• Bednets revisited- old idea, new angle.
• Bicoid by the numbers: quantifying a morphogen gradient.
• Changes in inflammatory processes associated with selective vulnerability following mild impairment of oxidative metabolism.
• Characterization of lipid A acylation patterns in Francisella tularensis, Francisella novicida, and Francisella philomiragia using multiple-stage mass spectrometry and matrix-assisted laser desorption/ionization on an intermediate vacuum source linear ion
• Chemotherapy disrupts activity of translational regulatory proteins in bone marrow stromal cells.
• Coordination and timing of spine and hip joints during full body reaching tasks.
• Ct31 hyperbaric oxygen in post-cardiac surgery stroke patients - the christchurch experience.
• Description of Triaenorhina burti n. sp. (Cestoda: Paruterinidae) from the Malabar trogon Harpactes fasciatus (Pennant) (Aves: Trogoniformes: Trogonidae) in Sri Lanka.
• Effect of carbohydrates on the production of thaxtomin A by Streptomyces acidiscabies.
• Epidermal growth factor receptor and transforming growth factor-beta signaling contributes to variation for wing shape in Drosophila melanogaster.
• Eyes, hands and ears in the diagnosis of heart disease in children.
• Identification of genes involved in the expression of atypical lipooligosaccharide structures from a second class of Haemophilus ducreyi.
• Iodine Deficiency Disorders (IDD) in the New Zealand population: another example of an outmoded IDD control programme.
• Lipid abnormalities in succinate semialdehyde dehydrogenase (Aldh5a1-/-) deficient mouse brain provide additional evidence for myelin alterations.
• Pathophysiology of red cell volume.
• Post-SARS public health law developments in Canada.
• Predictors of polyunsaturated fatty acid (PUFA) status in the first months of life.
• Resolution of the species problem in African trypanosomes.
• Responses of the mitochondrial alpha-ketoglutarate dehydrogenase complex to thiamine deficiency may contribute to regional selective vulnerability.
• The K1 serotype capsular polysaccharide of Porphyromonas gingivalis elicits chemokine production from murine macrophages that facilitates cell migration.
• The amino-conserved domain of human cytomegalovirus UL80a proteins is required for key interactions during early stages of capsid formation and virus production.
• The chemokine receptor homologue encoded by US27 of human cytomegalovirus is heavily glycosylated and is present in infected human foreskin fibroblasts and enveloped virus particles.
• The effect of infant diets supplemented with alpha-linolenic acid on growth and development: a systematic review and meta-analysis of randomised controlled trials.
• Therapeutic concepts in succinate semialdehyde dehydrogenase (SSADH; ALDH5a1) deficiency (gamma-hydroxybutyric aciduria). Hypotheses evolved from 25 years of patient evaluation, studies in Aldh5a1-/- mice and characterization of gamma-hydroxybutyric acid
• Those magnificient men in those flying machines--aviation medicine research at Farnborough in World War II.