Inhibition of glycogen synthase kinase-3 protects cells from intrinsic but not extrinsic oxidative stress

Taj D. King, Richard S. Jope

Research output: Contribution to journalArticle

54 Scopus citations


Oxidative stress is linked to neuronal dysfunction and death in many diseases. Glycogen synthase kinase-3 often promotes apoptosis, so this investigation tested whether glycogen synthase kinase-3 is linked to oxidative stress-induced apoptosis. Both intrinsic oxidative stress induced by the mitochondrial inhibitor rotenone and extrinsic oxidative stress induced by exogenously added H2O2 activated Bax, caspase-2, and caspase-3 in human neuroblastoma SH-SY5Y cells. Inhibitors of glycogen synthase kinase-3 blocked rotenone-induced, but not H2O2-induced, activation of both caspases, but not Bax activation. Thus, glycogen synthase kinase-3 is an important component of intrinsic oxidative stress-induced apoptosis that acts downstream of mitochondrial Bax activation, and there are substantial differences in the role of glycogen synthase kinase-3, and lithium's effects, in apoptotic signaling induced by intrinsic and extrinsic oxidative stress.

Original languageEnglish (US)
Pages (from-to)597-601
Number of pages5
Issue number6
StatePublished - Apr 25 2005
Externally publishedYes



  • Apoptosis
  • Glycogen synthase kinase-3
  • Hydrogen peroxide
  • Lithium
  • Oxidative stress
  • Rotenone

ASJC Scopus subject areas

  • Neuroscience(all)

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