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

Am J Physiol Cell Physiol. 2001 Nov;281(5):C1596-603. doi: 10.1152/ajpcell.2001.281.5.C1596.

Abstract

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.

Publication types

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

MeSH terms

  • 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

Substances

  • Caspase Inhibitors
  • Cytochrome c Group
  • DNA-Binding Proteins
  • E8 protein, Lycopersicon esculentum
  • Enzyme Inhibitors
  • Plant Proteins
  • Poly(ADP-ribose) Polymerases
  • CASP9 protein, human
  • Caspase 9
  • Caspases
  • Glucose