Role of reactive oxygen species and p53 in chromium(VI)-induced apoptosis

Citation
Jp. Ye et al., Role of reactive oxygen species and p53 in chromium(VI)-induced apoptosis, J BIOL CHEM, 274(49), 1999, pp. 34974-34980
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
274
Issue
49
Year of publication
1999
Pages
34974 - 34980
Database
ISI
SICI code
0021-9258(199912)274:49<34974:ROROSA>2.0.ZU;2-S
Abstract
Apoptosis is a programmed cell death mechanism to control cell number in ti ssues and to eliminate individual cells that may lead to disease states. Th e present study investigates chromium(VI) (Cr(VI))-induced apoptosis and th e role of reactive oxygen species (ROS) and p53 in this response, Treatment of human lung epithelial cells (A549) with Cr(VI) caused apoptosis as meas ured by DNA fragmentation, mitochondria damage, and cell morphology, Cr(VI) -induced apoptosis is contributed to ROS generation, resulting from cellula r reduction of Cr(VI) as measured by flow cytometric analysis of the staine d cells, oxygen consumption and electron spin resonance spin trapping Scave ngers of ROS, such as catalase, aspirin, and N-acetyl-L-cysteine, decreased Cr(VI)-induced apoptosis, whereas NADPH and glutathione reductase, enhance rs of Cr(VI)-induced BOS generation, increased it. p53 is activated by Cr(V I), mostly by ROS-mediated free radical reactions. Cr(VI)-induced ROS gener ation occurred within a few minutes after Cr(VI) treatment of the cells, wh ereas p53 induction took at least 5 h, The level of Cr(VI)-induced apoptosi s was similar in both p53-positive cells and p53-negative cells independent of p53 status in the early stage (0-3 h) of Cr(VI) treatment, However, at the later stage (3-24 h), the level of the apoptosis is higher in p53-posit ive cells than in p53-negative cells. These results suggest that ROS genera ted through Cr(VI) reduction is responsible to the early stage of apoptosis , whereas p53 contributes to the late stage of apoptosis and is responsible for the enhancement of Cr(VI)-induced apoptosis at this stage.