Document Detail

Impaired mitochondrial function results in increased tissue transglutaminase activity in situ.
MedLine Citation:
PMID:  11032884     Owner:  NLM     Status:  MEDLINE    
Tissue transglutaminase (tTG) is a transamidating enzyme that is elevated in Huntington's disease (HD) brain and may be involved in the etiology of the disease. Further, there is evidence of impaired mitochondrial function in HD. Therefore, in this study, we examined the effects of mitochondrial dysfunction on the transamidating activity of tTG. Neuroblastoma SH-SY5Y cells stably overexpressing human tTG or mutated inactive tTG were treated with 3-nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase. 3-NP treatment of tTG-expressing cells resulted in a significant increase of TG activity in situ. In vitro measurements demonstrated that 3-NP had no direct effect on tTG activity. However, 3-NP treatment resulted in a significant decrease of the levels of GTP and ATP, two potent inhibitors of the transamidating activity of tTG. No significant changes in the intracellular levels of calcium were observed in 3-NP-treated cells. Treatment with 3-NP in combination with antioxidants significantly reduced the 3-NP-induced increase in in situ TG activity, demonstrating that oxidative stress is a contributing factor to the increase of TG activity. This study demonstrates for the first time that impairment of mitochondrial function significantly increases TG activity in situ, a finding that may have important relevance to the etiology of HD.
M Lesort; J Tucholski; J Zhang; G V Johnson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  75     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-10-26     Completed Date:  2000-11-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1951-61     Citation Subset:  IM    
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0017, USA.
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MeSH Terms
Adenosine Triphosphate / metabolism
Antioxidants / pharmacology
Calcium / metabolism
Dose-Response Relationship, Drug
GTP-Binding Proteins / genetics,  metabolism*
Guanosine Triphosphate / metabolism
Huntington Disease / enzymology*
Marine Toxins / pharmacology
Mitochondria / drug effects,  metabolism*
Neuroblastoma / metabolism,  pathology
Nitro Compounds
Oxidative Stress / drug effects
Propionic Acids / pharmacology
Succinate Dehydrogenase / antagonists & inhibitors
Transglutaminases / genetics,  metabolism*
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Antioxidants; 0/Marine Toxins; 0/Nitro Compounds; 0/Oxocins; 0/Propionic Acids; 504-88-1/3-nitropropionic acid; 56-65-5/Adenosine Triphosphate; 59392-53-9/maitotoxin; 7440-70-2/Calcium; 86-01-1/Guanosine Triphosphate; EC Dehydrogenase; EC 2.3.2.-/transglutaminase 2; EC; EC 3.6.1.-/GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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