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Vanadate induces p53 transactivation through hydrogen peroxide and causes apoptosis.

Authors
Huang-C; Zhang-Z; Ding-M; Li-J; Ye-J; Leonard-SS; Shen-HM; Butterworth-L; Lu-Y; Costa-M; Rojanasakul-Y; Castranova-V; Vallyathan-V; Shi-X
Source
J Biol Chem 2000 Oct; 275(42):32516-32522
NIOSHTIC No.
20020703
Abstract
Vanadium is a metal widely distributed in the environment. Although vanadate-containing compounds exert potent toxic effects on a wide variety of biological systems, the mechanisms controlling vanadate-induced adverse effects remain to be elucidated. The present study investigated the vanadate-induced p53 activation and involvement of reactive oxygen species (ROS) in p53 activation as well as the role of p53 in apoptosis induction by vanadate. Exposure of mouse epidermal JB6 cells to vanadate led to transactivation of p53 activity in a time- and dose-dependent manner. It also caused mitochondrial damage, apoptosis, and generated ROS. Scavenging of vanadate-induced H(2)O(2) by N-acetyl-l-cysteine (a general antioxidant) or catalase (a specific H(2)O(2) inhibitor), or the chelation of vanadate by deferoxamine, resulted in inhibition of p53 activation and cell mitochondrial damage. In contract, an increase in H(2)O(2) generation in response to superoxide dismutase or NADPH enhanced these effects caused by vanadate. Furthermore, vanadate-induced apoptosis occurred in cells expressing wild-type p53 (p53+/+) but was very weak in p53-deficient (p53-/-) cells. These results demonstrate that vanadate induces p53 activation mainly through H(2)O(2) generation, and this activation is required for vanadate-induced apoptosis.
Keywords
Vanadium-compounds; Metals; Environmental-factors; Toxic-effects; Laboratory-animals; Animals; Animal-studies; Environmental-exposure
CODEN
JBCHA3
CAS No.
7440-62-2; 7722-84-1
Publication Date
20001020
Document Type
Journal Article
Email Address
xas0@cdc.gov
Fiscal Year
2001
NTIS Accession No.
NTIS Price
Issue of Publication
42
ISSN
0021-9258
NIOSH Division
HELD
Source Name
Journal of Biological Chemistry
State
WV; NY
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