Redox regulation of manganese superoxide dismutase.
Warner, Barabra B., Lorie Stuart, Sarah Gebb, Jonathan R.
Wisp[grave]e.
Children's Hospital Medical Center, Division of Pulmonary Biology,
Cincinnati, OH 45229-3039
APStracts 3:0035L, 1996.
The importance of reactive oxygen species (ROS), or changes in
cellular redox state in signal transduction and gene regulation is
becoming increasingly evident. In this paper we tested the hypothesis
that ROS are directly involved in the induction of the mitochondrial
antioxidant manganese superoxide dismutase (Mn-SOD), and mediate the
induction of Mn-SOD by TNF[alpha]. Pretreatment of human pulmonary
adenocarcinoma cells H441 with the antioxidants N-acetyl-L-cysteine
(NAC) and nordihydroguaiaretic acid (NDGA) blocked Mn-SOD induction
by TNFa, implicating ROS as a signaling agent in this pathway.
Treatment of H441 cells with the exogenous oxidants hydrogen peroxide
(H2O2) and diamide increased Mn-SOD mRNA, supporting the hypothesis
that ROS directly effect expression of Mn-SOD. The temporal pattern
of Mn-SOD induction differed for TNF[alpha] and H2O2, suggesting
distinct signalling pathways. DNA binding of two redox sensitive
transcription factors, NFkB and AP-1, was evaluated. TNF[alpha]
increased NFkB-DNA binding, an effect blocked by pretreatment with
NAC. H2O2 did not alter NFkB-DNA binding. There was no evidence of
AP-1 binding in either TNF[alpha] or H2O2 treated cells. We conclude
that ROS directly alter Mn-SOD expression, and are involved in the
induction of Mn-SOD by TNF[alpha].
Received 28 July 1995; accepted in final form 22 February 1996.
APS Manuscript Number L236-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96