The ataxia-telangiectasia gene product may modulate DNA turnover and control cell fate by regulating cellular redox in lymphocytes

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
M YanP K Wong

Abstract

The ATM kinase, when activated postnatally, exerts multiple functions to prevent the onset of ataxia-telangiectasia (AT). Using freshly isolated thymocytes from Atm-/- mice that were under stress during postnatal differentiation, we noted that thiol redox activity, as indicated by reduction of the tetrazolium MTS, and DNA turnover activity, as indicated by incorporation of [(3)H]thymidine into DNA, were both greatly increased compared with activities in thymocytes from Atm+/+ mice. This increased thymidine incorporation could be suppressed by the thiol N-acetylcysteine. In primary noncycling splenocytes, mitogens proportionally increased both the rate of [(3)H]thymidine incorporation and the rate of reduction of MTS. The mitogen-induced activities in splenocytes were not affected by ATM but were suppressed by the calcineurin-dependent inhibitor FK-506, which has no effect on these activities in thymocytes. These findings suggest that increased [(3)H]thymidine incorporation and reducing power indicate increased cell cycling in mitogenically stimulated splenocytes, whereas these two indicators represent increased FK-506-independent DNA turnover activities in thymocytes. Thus, a primary function of ATM is to activate the redox-sen...Continue Reading

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Citations

Dec 1, 2004·Cancer Chemotherapy and Pharmacology·Xianghong KuangPaul K Y Wong
Jun 29, 2013·Neuromolecular Medicine·Yu HuangMingshan Yan
Sep 27, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Anthony D D'SouzaGerald S Shadel
Jul 9, 2002·Clinical and Experimental Immunology·R SchubertS Zielen
Mar 11, 2010·Journal of Clinical Biochemistry and Nutrition·Tadayuki SakuragawaMakoto Suematsu
Apr 1, 2014·The Cerebellum·Ishani SahamaStephen Rose
Jan 21, 2012·Biochemical and Biophysical Research Communications·Xianghong KuangPaul K Y Wong
Apr 15, 2009·Biochemical and Biophysical Research Communications·Xianghong KuangMingshan Yan
Nov 27, 2007·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Ramune RelieneRobert H Schiestl
Aug 15, 2006·Pathologie-biologie·G MacéF Rosselli
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Sep 29, 2005·Laboratory Investigation; a Journal of Technical Methods and Pathology·Na LiuPaul K Y Wong
Jan 1, 2008·Clinical Medicine. Oncology·Ramune Reliene, Robert H Schiestl
Jun 21, 2003·The Journal of Biological Chemistry·Yasuaki Hiromasa, Thomas E Roche
Oct 15, 2020·Journal of Clinical Immunology·Tannaz Moeini ShadReza Yazdani
Dec 22, 2006·The Journal of Nutrition·Ramune Reliene, Robert H Schiestl

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