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

Moon Hee Lee, Dong Hoon Hyun, Karyn Ann Marshall, Lisa M. Ellerby, Dale E. Bredesen, Peter Jenner, Barry Halliwell

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

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 H2O2 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 NO2-/NO3- in the transfected cells and a fall in the level of nNOS protein.

Original languageEnglish
Pages (from-to)1550-1559
Number of pages10
JournalFree Radical Biology and Medicine
Volume31
Issue number12
DOIs
StatePublished - 15 Dec 2001

Keywords

  • Antioxidant defenses
  • Bcl-2
  • Free radicals
  • Nitric oxide synthase, Proteasome
  • Oxidative stress
  • Reactive nitrogen species

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