Hypoxia induces apoptosis via two independent pathways in Jurkat cells: differential regulation by glucose

Citation
R. Malhotra et al., Hypoxia induces apoptosis via two independent pathways in Jurkat cells: differential regulation by glucose, AM J P-CELL, 281(5), 2001, pp. C1596-C1603
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
ISSN journal
0363-6143 → ACNP
Volume
281
Issue
5
Year of publication
2001
Pages
C1596 - C1603
Database
ISI
SICI code
0363-6143(200111)281:5<C1596:HIAVTI>2.0.ZU;2-1
Abstract
Glucose uptake and metabolism inhibit hypoxia-induced apoptosis in a variet y of cell types, but the underlying molecular mechanisms remain poorly unde rstood. In the present study, we explore hypoxia-mediated cell death pathwa ys in Jurkat cells in the presence and absence of extracellular glucose. In the absence of extracellular glucose, hypoxia caused cytochrome c release, caspase 3 and poly(ADP-ribose) polymerase cleavage, and DNA fragmentation; this apoptotic response was blocked by the caspase 9 inhibitor z-LEHD-FMK. The presence of extracellular glucose during hypoxia prevented cytochrome c release and activation of caspase 9 but did not prevent apoptosis in Jurk at cells. In these conditions, overexpression of the caspase 8 inhibitor v- FLIP prevented hypoxia-mediated cell death. Thus hypoxia can stimulate two apoptotic pathways in Jurkat cells, one dependent on cytochrome c release f rom mitochondria that is prevented by glucose uptake and metabolism, and th e other independent of cytochrome c release and resulting from activation o f the death receptor pathway, which is accelerated by glucose uptake and me tabolism.