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Role of reactive oxygen species and p53 in chromium(VI)-induced apoptosis.
Ye J; Wang S; Leonard SS; Sun Y; Butterworth L; Antonini J; Ding M; Rojanasakul Y; Vallyathan V; Castranova V; Shi Xianglin
J Bio Chem 1999 Dec; 274(49):34974-34980
Apoptosis is a programmed cell death mechanism to control cell number in tissues and to eliminate individual cells that may lead to disease states. The present study investigates chromium(VI) (Cr(VI))-induced apoptosis and the role of reactive oxygen species (ROS) and p53 in this response. Treatment of human lung epithelial cells (A549) with Cr(VI) caused apoptosis as measured by DNA fragmentation, mitochondria damage, and cell morphology. Cr(VI)-induced apoptosis is contributed to ROS generation, resulting from cellular reduction of Cr(VI) as measured by flow cytometric analysis of the stained cells, oxygen consumption, and electron spin resonance spin trapping. Scavengers of ROS, such as catalase, aspirin, and N-acetyl-L-cysteine, decreased Cr(VI)-induced apoptosis, whereas NADPH and glutathione reductase, enhancers of Cr(VI)-induced ROS generation, increased it. p53 is activated by Cr(VI), mostly by ROS-mediated free radical reactions. Cr(VI)-induced ROS generation occurred within a few minutes after Cr(VI) treatment of the cells, whereas p53 induction took at least 5 h. The level of Cr(VI)-induced apoptosis 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-positive cells than in p53-negative cells. These results suggest that ROS generated 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.
In-vitro-studies; Chromium-compounds; Metabolites; Cell-damage; Cell-division
Pathology and Research Branch National Institute for Occupational Safety & Health 1095 Willowdale Rd Morgantown, WV 26505
Issue of Publication
Other Occupational Concerns
Journal of Biological Chemistry
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division