|Effects of aripiprazole and clozapine on the treatment of glycolytic carbon in PC12 cells.|
|PMID: 22392058 Owner: NLM Status: MEDLINE|
|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.|
|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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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-03-04|
|Title: Journal of neural transmission (Vienna, Austria : 1996) Volume: 119 ISSN: 1435-1463 ISO Abbreviation: J Neural Transm Publication Date: 2012 Nov|
|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|
|Languages: eng Pagination: 1327-42 Citation Subset: IM|
|Department of Physiology, Fujita Health University School of Medicine, Toyoake 470-1192, Japan. firstname.lastname@example.org|
|APA/MLA Format Download EndNote Download BibTex|
Adenosine Triphosphate / metabolism
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
|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 188.8.131.52/Isocitrate Dehydrogenase; EC 1.2.-/Ketone Oxidoreductases; EC 184.108.40.206/pyruvate dehydrogenase (NADP+); EC 220.127.116.11/Dihydrolipoamide Dehydrogenase; EC 18.104.22.168/Electron Transport Complex IV; EC 22.214.171.124/Hypoxanthine Phosphoribosyltransferase; EC 126.96.36.199/Protein-Serine-Threonine Kinases; EC 188.8.131.52/pyruvate dehydrogenase (acetyl-transferring) kinase|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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