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ATM-ROS-iNOS axis regulates nitric oxide mediated cellular senescence

Bagheri, Meisam and Nair, Raji R and Singh, Krishna Kumar and Saini, Deepak Kumar (2017) ATM-ROS-iNOS axis regulates nitric oxide mediated cellular senescence. In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1864 (1). pp. 177-190.

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Official URL: http://dx.doi.org/10.1016/j.bbamcr.2016.11.008

Abstract

Cellular senescence is an outcome of the accumulation of DNA damage which induces the growth arrest in cells. Physiologically, it is presumed to be mediated by accumulation of reactive oxygen species (ROS). Here, we show that another free radical, nitric oxide (NO) produced during inflammation or present as an environmental pollutant can also induce cellular senescence. In primary cells and various immortalized cell lines, exposure to chronic NO, through external addition or internally generated by iNOS expression, leads to the activation of DNA damage response and causes cellular senescence. The phenotype generated by NO includes robust growth arrest, increase in the levels of the DNA damage foci, ROS, SAS-gal staining, and inflammatory cytokines like IL-6 and IL-8, all hallmarks of cellular senescence similar to replicative senescence. Mechanistically, inhibitor and knockdown analysis revealed that NO mediates senescence through ATM kinase activation and the viability of cells is dependent on both ROS and ATM kinase involving the ATM-ROS-iNOS axis. Overall, we demonstrate that nitric oxide mediates cellular senescence through a novel free radical dependent genotoxic stress pathway. (C) 2016 Elsevier B.V. All rights reserved.

Item Type: Journal Article
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Additional Information: Copy right for this article belongs to the ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)
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Date Deposited: 31 Jan 2017 05:27
Last Modified: 31 Jan 2017 05:27
URI: http://eprints.iisc.ernet.in/id/eprint/56106

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