Document Detail


Effects of aripiprazole and clozapine on the treatment of glycolytic carbon in PC12 cells.
MedLine Citation:
PMID:  22392058     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Aripiprazole is the only atypical antipsychotic drug known to cause the phosphorylation of AMP-activated protein kinase (AMPK) in PC12 cells. However, the molecular mechanisms underlying this phosphorylation in aripiprazole-treated PC12 cells have not yet been clarified. Here, using PC12 cells, we show that these cells incubated for 24 h with aripiprazole at 50 μM and 25 mM glucose underwent a decrease in their NAD⁺/NADH ratio. Aripiprazole suppressed cytochrome c oxidase (COX) activity but enhanced the activities of pyruvate dehydrogenase (PDH), citrate synthase and Complex I. The changes in enzyme activities coincided well with those in NADH, NAD⁺, and NAD⁺/NADH ratio. However, the bioenergetic peril judged by the lowered COX activity might not be accompanied by excessive occurrence of apoptotic cell death in aripiprazole-treated cells, because the mitochondrial membrane potential was not decreased, but rather increased. On the other hand, when PC12 cells were incubated for 24 h with clozapine at 50 μM and 25 mM glucose, the NAD⁺/NADH ratio did not change. Also, the COX activity was decreased; and the PDH activity was enhanced. These results suggest that aripiprazole-treated PC12 cells responded to the bioenergetic peril more effectively than the clozapine-treated ones to return the ATP biosynthesis back toward its ordinary level. This finding might be related to the fact that aripiprazole alone causes phosphorylation of AMPK in PC12 cells.
Authors:
Akira Ota; Akira Nakashima; Yoko S Kaneko; Keiji Mori; Hiroshi Nagasaki; Takeshi Takayanagi; Mitsuyasu Itoh; Kazunao Kondo; Toshiharu Nagatsu; Miyuki Ota
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-04
Journal Detail:
Title:  Journal of neural transmission (Vienna, Austria : 1996)     Volume:  119     ISSN:  1435-1463     ISO Abbreviation:  J Neural Transm     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2013-04-18     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  9702341     Medline TA:  J Neural Transm     Country:  Austria    
Other Details:
Languages:  eng     Pagination:  1327-42     Citation Subset:  IM    
Affiliation:
Department of Physiology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan. aota@fujita-hu.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / metabolism
Adenosine Triphosphate / metabolism
Animals
Antipsychotic Agents / pharmacology*
Apoptosis / drug effects
Carbon / metabolism*
Cell Survival / drug effects
Clozapine / pharmacology*
Dihydrolipoamide Dehydrogenase / genetics,  metabolism
Dose-Response Relationship, Drug
Electron Transport Complex IV / metabolism
Extracellular Fluid / drug effects
Gene Expression Regulation, Enzymologic / drug effects*
Glucose / pharmacology
Glycolysis / drug effects*
Hypoxanthine Phosphoribosyltransferase / genetics,  metabolism
Isocitrate Dehydrogenase / genetics,  metabolism
Ketone Oxidoreductases / genetics,  metabolism
Lactic Acid / metabolism
Membrane Potential, Mitochondrial / drug effects
NAD / metabolism
Oxidoreductases / genetics,  metabolism
PC12 Cells / drug effects,  enzymology
Piperazines / pharmacology*
Protein-Serine-Threonine Kinases / genetics,  metabolism
Pyruvic Acid / metabolism
Quinolones / pharmacology*
RNA, Messenger / metabolism
Rats
Time Factors
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; 0/Piperazines; 0/Quinolones; 0/RNA, Messenger; 127-17-3/Pyruvic Acid; 50-21-5/Lactic Acid; 50-99-7/Glucose; 53-84-9/NAD; 56-65-5/Adenosine Triphosphate; 5786-21-0/Clozapine; 58-64-0/Adenosine Diphosphate; 7440-44-0/Carbon; 82VFR53I78/aripiprazole; EC 1.-/Oxidoreductases; EC 1.1.1.41/Isocitrate Dehydrogenase; EC 1.2.-/Ketone Oxidoreductases; EC 1.2.1.51/pyruvate dehydrogenase (NADP+); EC 1.8.1.4/Dihydrolipoamide Dehydrogenase; EC 1.9.3.1/Electron Transport Complex IV; EC 2.4.2.8/Hypoxanthine Phosphoribosyltransferase; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.2/pyruvate dehydrogenase (acetyl-transferring) kinase

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


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