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

Hyun Eui Kim, So Young Yoon, Jung Eun Lee, Won Seok Choi, Byung K. Jin, T. H. Oh, George J. Markelonis, Sang Yearn Chun, Young J. Oh

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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 μM 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.

Original languageEnglish
Pages (from-to)659-665
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume286
Issue number3
DOIs
Publication statusPublished - 2001

Bibliographical note

Funding Information:
The authors gratefully acknowledge Dr. A. Heller at the University of Chicago for providing us with the MN9D cell line. This work was supported by HMP-00-CH-13-0012, and partly by the KOSEF through the Brain Research Center and 1999-2-207-007-3 and FG-4-04 of 21C Frontier Program for Functional Analysis of Human Genome from MOST (to Y.J.O.).

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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