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Glutathione levels and sensitivity to apoptosis are regulated by changes in transaldolase expression.
J Biol Chem. 1996 Dec 20; 271(51):32994-3001.JB

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 ROIs in each pathway tested. Production of ROIs in Fas-mediated cell death was further substantiated by measurement of intracellular ROI production with oxidation-sensitive fluorescent probes, by the protective effects of GSH precursor, N-acetyl cysteine, free radical spin traps 5,5-dimethyl-1-pyrroline-1-oxide and 3,3,5,5-tetramethyl-1-pyrroline-1-oxide, the antioxidants desferrioxamine, nordihydroguaiaretic acid, and Amytal, and by the enhancing effects of GSH depletion with buthionine sulfoximine. The results provide definitive evidence that TAL has a role in regulating the balance between the two branches of PPP and its overall output as measured by GSH production and thus influences sensitivity to cell death signals.

Authors+Show Affiliations

Department of Pathology, State University of New York Health Science Center, College of Medicine, Syracuse, New York 13210, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8955144

Citation

Banki, K, et al. "Glutathione Levels and Sensitivity to Apoptosis Are Regulated By Changes in Transaldolase Expression." The Journal of Biological Chemistry, vol. 271, no. 51, 1996, pp. 32994-3001.
Banki K, Hutter E, Colombo E, et al. Glutathione levels and sensitivity to apoptosis are regulated by changes in transaldolase expression. J Biol Chem. 1996;271(51):32994-3001.
Banki, K., Hutter, E., Colombo, E., Gonchoroff, N. J., & Perl, A. (1996). Glutathione levels and sensitivity to apoptosis are regulated by changes in transaldolase expression. The Journal of Biological Chemistry, 271(51), 32994-3001.
Banki K, et al. Glutathione Levels and Sensitivity to Apoptosis Are Regulated By Changes in Transaldolase Expression. J Biol Chem. 1996 Dec 20;271(51):32994-3001. PubMed PMID: 8955144.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glutathione levels and sensitivity to apoptosis are regulated by changes in transaldolase expression. AU - Banki,K, AU - Hutter,E, AU - Colombo,E, AU - Gonchoroff,N J, AU - Perl,A, PY - 1996/12/20/pubmed PY - 1996/12/20/medline PY - 1996/12/20/entrez SP - 32994 EP - 3001 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 271 IS - 51 N2 - 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 ROIs in each pathway tested. Production of ROIs in Fas-mediated cell death was further substantiated by measurement of intracellular ROI production with oxidation-sensitive fluorescent probes, by the protective effects of GSH precursor, N-acetyl cysteine, free radical spin traps 5,5-dimethyl-1-pyrroline-1-oxide and 3,3,5,5-tetramethyl-1-pyrroline-1-oxide, the antioxidants desferrioxamine, nordihydroguaiaretic acid, and Amytal, and by the enhancing effects of GSH depletion with buthionine sulfoximine. The results provide definitive evidence that TAL has a role in regulating the balance between the two branches of PPP and its overall output as measured by GSH production and thus influences sensitivity to cell death signals. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/8955144/Glutathione_levels_and_sensitivity_to_apoptosis_are_regulated_by_changes_in_transaldolase_expression_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=8955144 DB - PRIME DP - Unbound Medicine ER -