GLUT-1 reduces hypoxia-induced apoptosis and JNK pathway activation

Zhiwu Lin, Joel M. Weinberg, Ricky Malhotra, Steven E. Merritt, Lawrence B. Holzman, Frank C. Brosius

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Many studies have suggested that enhanced glucose uptake protects cells from hypoxic injury. More recently, it has become clear that hypoxia induces apoptosis as well as necrotic cell death. We have previously shown that hypoxia-induced apoptosis can be prevented by glucose uptake and glycolytic metabolism in cardiac myocytes. To test whether increasing the number of glucose transporters on the plasma membrane of cells could elicit a similar protective response, independent of the levels of extracellular glucose, we overexpressed the facilitative glucose transporter GLUT-1 in a vascular smooth muscle cell line. After 4 h of hypoxia, the percentage of cells that showed morphological changes of apoptosis was 30.5 ± 2.6% in control cells and only 6.0 ± 1.1 and 3.9 ± 0.3% in GLUT-1-overexpressing cells. Similar protection against cell death and apoptosis was seen in GLUT-1-overexpressing cells treated for 6 h with the electron transport inhibitor rotenone. In addition, hypoxia and rotenone stimulated c-Jun-NH2-terminal kinase (JNK) activity > 10-fold in control cell lines, and this activation was markedly reduced in GLUT-1-overexpressing cell lines. A catalytically inactive mutant of MEKK1, an upstream kinase in the JNK pathway, reduced hypoxia-induced apoptosis by 39%. These findings show that GLUT-1 overexpression prevents hypoxia-induced apoptosis possibly via inhibition of stress-activated protein kinase pathway activation.

Original languageEnglish (US)
Pages (from-to)E958-E966
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5 41-5
StatePublished - May 2000
Externally publishedYes


  • Facilitative glucose transport
  • Mitogen- activated protein kinase
  • Necrosis
  • Stress-activated protein kinase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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