Effect of overexpression of BCL-2 on cellular oxidative damage, nitric oxide production, antioxidant defenses, and the proteasome

Free Radic Biol Med. 2001 Dec 15;31(12):1550-9. doi: 10.1016/s0891-5849(01)00633-5.


Bcl-2 is a gene family involved in the suppression of apoptosis in response to a wide range of cellular insults. Multiple papers have suggested a link between Bcl-2 and oxidative damage/antioxidant protection. We therefore examined parameters of antioxidant defense and oxidative damage in two different cell lines, NT-2/D1 (NT-2) and SK-N-MC, overexpressing Bcl-2 as compared with vector-only controls. Bcl-2 transfectants of both cell lines were more resistant to H(2)O(2) and showed increases in GSH level and Cu/Zn-superoxide dismutase (SOD1) activity, but not in Mn-superoxide dismutase, glutathione peroxidase, or glutathione reductase activities. Catalase activity was increased in SK-N-MC cells. Overexpression of Bcl-2 did not significantly decrease levels of oxidative DNA damage (measured as 8-hydroxyguanine) or lipid peroxidation, but it decreased levels of 3-nitrotyrosine in both cell lines and protein carbonyls in SK-N-MC cells only. It also increased proteasome activity in both cell lines. We conclude that Bcl-2 raises cellular antioxidant defense status, but this is not necessarily reflected in decreased levels of oxidative damage to DNA and lipids. The ability of Bcl-2 overexpression to decrease 3-nitrotyrosine levels suggests that it may decrease formation of peroxynitrite or other reactive nitrogen species; this was confirmed as decreased production of NO(2)(-)/NO(3)(-) in the transfected cells and a fall in the level of nNOS protein.

MeSH terms

  • Antioxidants / metabolism*
  • Cell Survival / physiology
  • Cysteine Endopeptidases / metabolism*
  • Enzyme Activation
  • Glutathione / metabolism
  • Humans
  • Male
  • Multienzyme Complexes / metabolism*
  • Neoplasms, Nerve Tissue
  • Neuroblastoma
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Oxidative Stress / physiology
  • Proteasome Endopeptidase Complex
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Reactive Nitrogen Species / metabolism
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Teratocarcinoma
  • Testicular Neoplasms
  • Transfection
  • Tumor Cells, Cultured
  • Up-Regulation


  • Antioxidants
  • Multienzyme Complexes
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Nitrogen Species
  • SOD1 protein, human
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Glutathione