Vanadate induces p53 transactivation through hydrogen peroxide and causes apoptosis

Citation
Cs. Huang et al., Vanadate induces p53 transactivation through hydrogen peroxide and causes apoptosis, J BIOL CHEM, 275(42), 2000, pp. 32516-32522
Citations number
48
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
275
Issue
42
Year of publication
2000
Pages
32516 - 32522
Database
ISI
SICI code
0021-9258(20001020)275:42<32516:VIPTTH>2.0.ZU;2-T
Abstract
Vanadium is a metal widely distributed in the environment. Although vanadat e-containing compounds exert potent toxic effects on a wide variety of biol ogical systems, the mechanisms controlling vanadate-induced adverse effects remain to be elucidated. The present study investigated the vanadate-induc ed p53 activation and involvement of reactive oxygen species (ROS) in p53 a ctivation as well as the role of p53 in apoptosis induction by vanadate. Ex posure of mouse epidermal JB6 cells to vanadate led to transactivation of p 53 activity in a time- and dose-dependent manner. It also caused mitochondr ial damage, apoptosis, and generated ROS. Scavenging of vanadate-induced H2 O2 by N-acetyl-L-cysteine (a general antioxidant) or catalase (a specific H 2O2 inhibitor), or the chelation of vanadate by deferoxamine, resulted in i nhibition of p53 activation and cell mitochondrial damage. In contract, an increase in H2O2 generation in response to superoxide dismutase or NADPH en hanced these effects caused by vanadate. Furthermore, vanadate-induced apop tosis occurred in cells expressing wild-type p53 (p53+/+) but was very weak in p53-deficient (p53-/-) cells. These results demonstrate that vanadate i nduces p53 activation mainly through H2O2 generation, and this activation i s required for vanadate-induced apoptosis.