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Molecular ordering in HIV-induced apoptosis. Oxidative stress, activation of caspases, and cell survival are regulated by transaldolase.
J Biol Chem. 1998 May 08; 273(19):11944-53.JB

Abstract

Dysregulated apoptosis may underlie the etiology of T cell depletion by human immunodeficiency virus type 1 (HIV-1). We show that HIV-induced apoptosis is preceded by an exponential increase in reactive oxygen intermediates (ROIs) produced in mitochondria. This leads to caspase-3 activation, phosphatidylserine (PS) externalization, and GSH depletion. Since mitochondrial ROI levels are regulated by the supply of NADPH from the pentose phosphate pathway (PPP), the effect of transaldolase (TAL), a key enzyme of PPP, was investigated. Jurkat and H9 human CD4+ T cells were transfected with TAL expression vectors oriented in the sense or antisense direction. TAL overexpression down-regulated glucose-6-phosphate dehydrogenase activities and GSH levels. Alternatively, decreased TAL expression up-regulated glucose-6-phosphate dehydrogenase activities and GSH levels. HIV-induced 1) mitochondrial ROI production, 2) caspase-3 activation, 3) proteolysis of poly(ADP-ribose) polymerase, and 4) PS externalization were accelerated in cells overexpressing TAL. In contrast, suppression of TAL abrogated these four activities. Thus, susceptibility to HIV-induced apoptosis can be regulated by TAL through controlling the balance between mitochondrial ROI production and the metabolic supply of reducing equivalents by the PPP. The dominant effect of TAL expression on oxidative stress, caspase activation, PS externalization, and cell death suggests that this balance plays a pivotal role in HIV-induced apoptosis.

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 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

9565623

Citation

Banki, K, et al. "Molecular Ordering in HIV-induced Apoptosis. Oxidative Stress, Activation of Caspases, and Cell Survival Are Regulated By Transaldolase." The Journal of Biological Chemistry, vol. 273, no. 19, 1998, pp. 11944-53.
Banki K, Hutter E, Gonchoroff NJ, et al. Molecular ordering in HIV-induced apoptosis. Oxidative stress, activation of caspases, and cell survival are regulated by transaldolase. J Biol Chem. 1998;273(19):11944-53.
Banki, K., Hutter, E., Gonchoroff, N. J., & Perl, A. (1998). Molecular ordering in HIV-induced apoptosis. Oxidative stress, activation of caspases, and cell survival are regulated by transaldolase. The Journal of Biological Chemistry, 273(19), 11944-53.
Banki K, et al. Molecular Ordering in HIV-induced Apoptosis. Oxidative Stress, Activation of Caspases, and Cell Survival Are Regulated By Transaldolase. J Biol Chem. 1998 May 8;273(19):11944-53. PubMed PMID: 9565623.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular ordering in HIV-induced apoptosis. Oxidative stress, activation of caspases, and cell survival are regulated by transaldolase. AU - Banki,K, AU - Hutter,E, AU - Gonchoroff,N J, AU - Perl,A, PY - 1998/6/13/pubmed PY - 1998/6/13/medline PY - 1998/6/13/entrez SP - 11944 EP - 53 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 273 IS - 19 N2 - Dysregulated apoptosis may underlie the etiology of T cell depletion by human immunodeficiency virus type 1 (HIV-1). We show that HIV-induced apoptosis is preceded by an exponential increase in reactive oxygen intermediates (ROIs) produced in mitochondria. This leads to caspase-3 activation, phosphatidylserine (PS) externalization, and GSH depletion. Since mitochondrial ROI levels are regulated by the supply of NADPH from the pentose phosphate pathway (PPP), the effect of transaldolase (TAL), a key enzyme of PPP, was investigated. Jurkat and H9 human CD4+ T cells were transfected with TAL expression vectors oriented in the sense or antisense direction. TAL overexpression down-regulated glucose-6-phosphate dehydrogenase activities and GSH levels. Alternatively, decreased TAL expression up-regulated glucose-6-phosphate dehydrogenase activities and GSH levels. HIV-induced 1) mitochondrial ROI production, 2) caspase-3 activation, 3) proteolysis of poly(ADP-ribose) polymerase, and 4) PS externalization were accelerated in cells overexpressing TAL. In contrast, suppression of TAL abrogated these four activities. Thus, susceptibility to HIV-induced apoptosis can be regulated by TAL through controlling the balance between mitochondrial ROI production and the metabolic supply of reducing equivalents by the PPP. The dominant effect of TAL expression on oxidative stress, caspase activation, PS externalization, and cell death suggests that this balance plays a pivotal role in HIV-induced apoptosis. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/9565623/Molecular_ordering_in_HIV_induced_apoptosis__Oxidative_stress_activation_of_caspases_and_cell_survival_are_regulated_by_transaldolase_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9565623 DB - PRIME DP - Unbound Medicine ER -