Vanadate Induces p53 Transactivation through Hydrogen Peroxide and Causes Apoptosis

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

Down regulation of p53 with HPV E6 delays and modifies cell death in oxidant response of human diploid fibroblasts: an apoptosis-like cell death associated with mitosis

“…This postulation is supported by several recent reports showing a role of p53 in regulating mitochondrial cytochrome c release and early activation of caspases (Ding et al, 1998;Lee, 1998;Li et al, 1999;Moll and Zaika, 2001;Schuler et al, 2000). Nevertheless, regardless of whether or not p53 is present, oxidants can cause mitochondrial cytochrome c release by disturbing mitochondrial function (Huang et al, 2000a;Quillet-Mary et al, 1997;Stridh et al, 1998;Tada-Oikawa et al, 1999). Cytochrome c in the cytosol activates caspase-9 after binding to Apaf-1 and initiates a cascade proteolytic cleavage.…”

Vanadate oligomers: In vivo effects in hepatic vanadium accumulation and stress markers

“…1). Even though vanadium may participate in Fenton-like reactions [9], together with the proposed mechanisms of vanadate action that involves its bioreduction and ROS production [15,18,19,40], our results point out to a depression in the overall rate of ROS production. This observation is in good agreement with previous reports showing that vanadate supplementation diminished oxidative stress in certain experimental conditions, such as in rat-induced hepatocarcinogenesis [23] and in rat diabetic tissues [41].…”

“…Thus, decameric vanadate species induced changes in O ÅÀ 2 mitochondrial production opposite to those produced by the oligomeric vanadate species that are present in metavanadate solution, from which we can suggest again different pathways of biological action for the different oligomers. Several proposed vanadate action pathways within cells involves O ÅÀ 2 production mediated by NADPH oxido-reductases from the respiratory chain [15,18,19,40]. If we consider the action and detoxification mechanism proposed for vanadate, where vanadate is reduced to vanadyl with production of O ÅÀ 2 , it is possible that decavanadate participates in such reactions in a different manner.…”

“…Moreover, vanadium toxicological effects in several cell types have been related with ROS production [16][17][18][19]. Nevertheless, vanadium was recently reviewed as ''an element of atypical biological significance'' [20], due to insulin mimetic properties of vanadium [16,21,22] and to the preventive effects of vanadium against animal carcinogens [23][24][25][26].…”

Ascochlorin activates p53 in a manner distinct from DNA damaging agents

“…Respiratory inhibitors produce reactive oxygen species in mitochondria. 42 Reactive oxygen species 43,44 and generators of reactive oxygen species 45,46 have been reported to activate p53. However, reactive oxygen species phosphorylate serines 15 and 20.…”