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

• Published in: American Journal of Physiology: Cell Physiology 2001-11, Vol.281 (5), p.C1596-C1603
• Main Authors: Malhotra, Ricky, Lin, Zhiwu, Vincenz, Claudius, Brosius, Frank C., III
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Apoptosis - physiology; Blotting, Western; Caspase 9; Caspase Inhibitors; Caspases - metabolism; Cell Hypoxia - drug effects; Cell Hypoxia - physiology; Cytochrome c Group - antagonists & inhibitors; Cytochrome c Group - metabolism; DNA Fragmentation; DNA-Binding Proteins; Enzyme Activation - physiology; Enzyme Inhibitors - pharmacology; Glucose - metabolism; Glucose - physiology; Humans; Jurkat Cells; Mitochondria - physiology; Plant Proteins - biosynthesis; Poly(ADP-ribose) Polymerases - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Space life sciences
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.2001.281.5.c1596

Division of Nephrology, Departments of 1  Internal Medicine and 2  Pathology, University of Michigan Medical School and Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan 48109 Glucose uptake and metabolism inhibit hypoxia-induced apoptosis in a variety of cell types, but the underlying molecular mechanisms remain poorly understood. In the present study, we explore hypoxia-mediated cell death pathways 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 Jurkat 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 from mitochondria that is prevented by glucose uptake and metabolism, and the other independent of cytochrome c release and resulting from activation of the death receptor pathway, which is accelerated by glucose uptake and metabolism. cytochrome c ; viral FLICE inhibitory protein; death receptor; caspases