Apoptosis

, Volume 10, Issue 3, pp 657–665

Evidence for a non-antioxidant, dose-dependent role of α -lipoic acid in caspase-3 and ERK2 activation in endothelial cells

Authors

  • S. A. Marsh
    • School of Human Movement StudiesThe University of Queensland
  • B. K. Pat
    • School of Human Movement StudiesThe University of Queensland
  • G. C. Gobe
    • School of Human Movement StudiesThe University of Queensland
    • School of Human Movement StudiesThe University of Queensland
    • School of Human Movement StudiesThe University of Queensland
Article

DOI: 10.1007/s10495-005-1901-4

Cite this article as:
Marsh, S.A., Pat, B.K., Gobe, G.C. et al. Apoptosis (2005) 10: 657. doi:10.1007/s10495-005-1901-4

Abstract

Endothelial cell apoptosis contributes to atherosclerosis and may be exacerbated by oxidative stress. Results from clinical trials using antioxidant supplementation are equivocal and could be enhanced by antioxidants with additional non-antioxidant properties such as α -lipoic acid and α -tocopherol. The aim of this study was to investigate the effects of these antioxidants on cytoprotective pathways and endothelial apoptosis. Endothelial cells were incubated with α -lipoic acid and α -tocopherol, alone or in combination, prior to incubation with H2O2 or staurosporine. α -lipoic acid pre-treatment alone increased caspase-3 activity in a dose-dependent manner. Both H2O2 and staurosporine increased DNA fragmentation and caspase-3 activity and pre-treatment of cells with α -lipoic acid and/or α -tocopherol failed to prevent stress-induced apoptosis. Neither antioxidant treatments nor apoptotic inducers alone altered expressions of Bcl-2, Bax, HSP70 or pERK1/2 or pJNK. α -lipoic decreased pERK2 in staurosporine-treated cells in a dose-dependent manner. These findings indicate that pre-incubation with α -lipoic acid and α -tocopherol, alone or in combination, does not protect against oxidative- or non-oxidative-induced apoptosis in endothelial cells. Moreover, we have demonstrated a non-antioxidant, dose-dependent role of α -lipoic acid in caspase-3 and ERK2 activation. These data provide an insight and indicate caution in the use of high doses of α -lipoic acid as an antioxidant.

Keywords

α-lipoic acidα-tocopherolendotheliumoxidative stress
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Copyright information

© Springer Science + Business Media, Inc. 2005