Disrupted mitochondrial electron transport function increases expression of anti-apoptotic bcl-2 and bcl-X(L) proteins in SH-SY5Y neuroblastoma and in Parkinson disease cybrid cells through oxidative stress

J Neurosci Res. 2000 Sep 15;61(6):693-700. doi: 10.1002/1097-4547(20000915)61:6<693::AID-JNR13>3.0.CO;2-4.


Death of dopamine neurons in Parkinson disease (PD) may arise from consequences of the complex I (C-I) defect in the mitochondrial electron transport chain (ETC). Whether cells activate programmed death (apoptosis) pathways derives, in part, from relative activities of proteins such as bcl-2 and bcl-X(L), that have anti-apoptotic actions. We studied the responses of bcl-2 and bcl-X(L) genes in pharmacologic (acute incubation with methylpyridinium (MPP+)) and mitochondrial transgenic ("cybrid") models of Parkinson disease C-I defects. MPP+ incubation increased levels of bcl-2 and bcl-X(L) proteins in native SH-SY5Y cells but not in rho(0) cells devoid of ETC activity. MPP+ increased bcl-2 mRNA levels by 40% at 8 hr. Confocal microscopic imaging showed that the intracellular distribution of immunoreactive bcl-2 was not significantly associated with mitochondrial membranes at baseline but was associated with mitochondria after 12 hr of MPP+. Immunoreactive bcl-X(L) protein was significantly and equally associated with mitochondrial membranes both at baseline and after MPP+. PD cybrids showed increased basal levels of bcl-2 and bcl-X(L) proteins, similar to the maximum levels found after MPP+ treatment of control SY5Y cells. After MPP+ exposure, bcl-2 protein levels increased in control cybrids but did not increase further in PD cybrids. Both pharmacologically generated and transgenically induced C-I inhibition increases levels of anti-apoptotic bcl proteins, possibly from increased gene transcription. Augmentation of bcl-2 and bcl-X(L) expression may delay neurodegeneration in PD.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-4-phenylpyridinium / pharmacology
  • Apoptosis / physiology
  • DNA, Mitochondrial / genetics
  • Electron Transport / drug effects
  • Electron Transport / physiology*
  • Gene Expression Regulation / drug effects
  • Herbicides / pharmacology
  • Humans
  • Hybrid Cells
  • Microscopy, Confocal
  • Mitochondria / physiology*
  • Neuroblastoma
  • Neurons / chemistry
  • Neurons / cytology
  • Neurons / metabolism
  • Oxidative Stress / physiology*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured
  • bcl-X Protein


  • BCL2L1 protein, human
  • DNA, Mitochondrial
  • Herbicides
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-X Protein
  • 1-Methyl-4-phenylpyridinium