6 144

Cited 15 times in

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

Kim, HE; Yoon, SY; Lee, JE; Choi, WS; Jin, BK; Oh, TH; Markelonis, GJ; Chun, SY; Oh, YJ
Biochemical and biophysical research communications, 286(3):659-665, 2001
Journal Title
Biochemical and biophysical research communications
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
Appears in Collections:
Journal Papers > Research Organization > Institute for Medical Sciences
AJOU Authors
진, 병관
Full Text Link
RIS (EndNote)
XLS (Excel)


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.