Glutathione levels and sensitivity to apoptosis are regulated by changes in transaldolase expression.

The Journal of Biological Chemistry
K BankiA Perl

Abstract

Transaldolase (TAL) is a key enzyme of the reversible nonoxidative branch of the pentose phosphate pathway (PPP) that is responsible for the generation of NADPH to maintain glutathione at a reduced state (GSH) and, thus, to protect cellular integrity from reactive oxygen intermediates (ROIs). Formation of ROIs have been implicated in certain types of apoptotic cell death. To evaluate the role of TAL in this process, Jurkat human T cells were permanently transfected with TAL expression vectors oriented in the sense or antisense direction. Overexpression of TAL resulted in a decrease in glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities and NADPH and GSH levels and rendered these cells highly susceptible to apoptosis induced by serum deprivation, hydrogen peroxide, nitric oxide, tumor necrosis factor-alpha, and anti-Fas monoclonal antibody. In addition, reduced levels of TAL resulted in increased glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities and increased GSH levels with inhibition of apoptosis in all five model systems. The effect of TAL expression on susceptibility to apoptosis through regulating the PPP and GSH production is consistent with an involvement of RO...Continue Reading

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Citations

Jul 9, 1999·Journal of Biomedical Materials Research·H NygrenI Lundström
Jan 31, 2002·Arthritis and Rheumatism·Peter GergelyAndras Perl
Jul 13, 2002·Arthritis and Rheumatism·Gary M KammerGeorge C Tsokos
Nov 7, 2008·Journal of Inherited Metabolic Disease·M M C WamelinkC Jakobs
Jan 15, 2013·Journal of Inherited Metabolic Disease·Wafaa EyaidFowzan S Alkuraya
Jun 25, 2002·Molecular Aspects of Medicine·Malcolm J JacksonSiân B Astley
May 23, 2002·Biochimie·Christophe FleuryJean-Luc Vayssière
Jul 28, 2011·Journal of Proteome Research·Iosif VranakisAnna Psaroulaki
Aug 8, 2009·Cell Death and Differentiation·R Franco, J A Cidlowski
Oct 9, 2013·Nature Reviews. Rheumatology·Andras Perl
Jul 20, 2002·Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine·A OrzechowskiJ Fuller
Jan 8, 2011·The Journal of Biological Chemistry·Ali TebbiMichel Lepoivre
Dec 14, 2012·The Journal of Biological Chemistry·Eunsook S JinCraig R Malloy
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Sep 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Andras PerlKatalin Banki
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Sep 3, 2013·Journal of Proteomics·Aishwarya Anand RaoSanjeeva Srivastava
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May 15, 2012·Free Radical Biology & Medicine·Chiara RigantiDario Ghigo

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis