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MPP(+) downregulates mitochondrially encoded gene transcripts and their activities in dopaminergic neuronal cells: protective role of Bcl-2.

Authors
Kim, HE; Yoon, SY; Lee, JE; Choi, WS; Jin, BK; Oh, TH; Markelonis, GJ; Chun, SY; Oh, YJ
Citation
Biochemical and biophysical research communications, 286(3):659-665, 2001
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
Abstract
The effects of neurotoxins on levels of mitochondrially encoded gene transcripts in a dopaminergic neuronal cell line, MN9D, were examined following treatment with 200 microM N-methyl-4-phenylpyridinium (MPP(+)) or 6-hydroxydopamine (6-OHDA). As confirmed by a Northern blot analysis, levels of cytochrome c oxidase subunit 3 (COX III) and ATPase subunit 6 (ATPase 6) transcript were decreased in a time-dependent manner following treatment with MPP(+) but not with 6-OHDA. Accordingly, enzymatic activity of cytochrome c oxidase (COX) and the intracellular ATP content were also decreased in MPP(+)-treated cells while these remained unaltered in 6-OHDA-treated cells. In the cell death paradigm induced by MPP(+), overexpression of Bcl-2 in MN9D cells (MN9D/Bcl-2) significantly blocked MPP(+)-induced downregulation of COX III and ATPase 6 transcripts. In MN9D/Bcl-2 cells, MPP(+)-induced downregulation of COX activity and the intracellular level of ATP was also blocked. Treatment with a pan-caspase inhibitor, however, neither prevented MPP(+)-induced downregulation of COX activity nor affected intracellular level of ATP in MN9D cells. Taken together, our present data suggest that Bcl-2 may play a regulatory role in energy metabolism by preventing downregulation of mitochondrially encoded gene(s) at a point distinct from its known anticaspase activity in MPP(+)-induced dopaminergic neuronal death.
MeSH terms
1-Methyl-4-phenylpyridinium/pharmacology*Adenosine Triphosphatases/biosynthesisAdenosine Triphosphatases/geneticsAdenosine Triphosphate/metabolismAnimalsCell DeathCell LineDNA, Mitochondrial/geneticsDopamine Agents/pharmacology*Down-RegulationElectron Transport Complex IV/geneticsElectron Transport Complex IV/metabolismMitochondria/enzymology*Mitochondria/genetics*Mitochondrial Proton-Translocating ATPasesNeurons/drug effectsNeurons/metabolism*Oxidopamine/pharmacologyProto-Oncogene Proteins c-bcl-2/geneticsProto-Oncogene Proteins c-bcl-2/physiology*RNA, Messenger/biosynthesisTranscription, Genetic/drug effectsTransfection
DOI
10.1006/bbrc.2001.5446
PMID
11511111
Appears in Collections:
Journal Papers > Research Organization > Institute for Medical Sciences
AJOU Authors
진, 병관
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