NDLI: Role of reactive oxygen species and Cr(VI) in Ras-mediated signal transduction

Content Provider	Springer Nature Link
Author	Wang, Suwei Leonard, Stephen S. Ye, Jianping Gao, Ning Wang, Liying Shi, Xianglin
Copyright Year	2004
Abstract	Previous studies have shown that a constitutively active isoform of Ras is able to produce superoxide radical (O$_{2}$ $^{−}$). The present study investigate the mechanisms by which O$_{2}$ $^{−}$ radical mediates signals from Ras protein to the nucleus, leading to cellular responses such as apoptosis in Cr(VI)-stimulated cells. Two human prostate tumor cell lines, Ras(+), which overexpresses Ras, and Ras(−), which has a normal Ras level, were utilized. Compared to Ras(−) cells, Ras(+) cells exhibited higher susceptibility to apoptosis induced by Cr(VI). Catalase, sodium formate, and deferoxamine inhibited Cr(VI)-induced apoptosis. Similar differences were observed in both cellular DNA damage and the activation of p53 protein. The differences in Cr(VI)-induced cell responses in Ras(+) and Ras(−) cells were due to differences in the generation of free radicals between these two cells. ESR spin trapping measurements showed that Ras(+) cells generated more hydroxyl radical (·OH), O$_{2}$ $^{−}$ radical, and Cr(V) than Ras(−) cells following Cr(VI) stimulation. The generation of the reactive oxygen species (ROS) can be abolished by the addition of superoxide dismutase (SOD) or if the experiment were carried out in an argon atmosphere. Catalase inhibited spin adduct signals but was much less potent than SOD. The mechanism of ROS generation in Cr(VI)-stimulated Ras(+) cells involves the reduction of molecular oxygen to O$_{2}$ $^{−}$ radical by a flavoenzyme-containing NADPH oxidase complex as shown by oxygen consumption and diphenylene iodonium (DPI) inhibition. Results shown above support the following conclusions: (a) Ras protein mediates O$_{2}$ $^{−}$ radical generation through reduction of molecular oxygen by NADPH oxidase in Cr(VI)-stimulated cells. (b) The O$_{2}$ $^{−}$ radical and Cr(VI) produce other reactive species, including H$_{2}$O$_{2}$, ·OH radical, and Cr(V) through O$_{2}$ $^{−}$ dismutation and Haber-Weiss type of reactions. (c) Among these reactive species, ·OH radical is responsible for the further transduction of signals from Ras to the nucleus, leading to various cell responses.
Starting Page	119
Ending Page	127
Page Count	9
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	255
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2004-01-01
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cardiology Medical Biochemistry Oncology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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