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

Ricky Malhotra, Zhiwu Lin, Claudius Vincenz, Frank C. Brosius

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)C1596-C1603
JournalAmerican Journal of Physiology - Cell Physiology
Issue number5 50-5
StatePublished - 2001
Externally publishedYes


  • Caspases
  • Cytochrome c
  • Death receptor
  • Viral FLICE inhibitory protein

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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