AMP-activated protein kinase is essential for survival in chronic hypoxia

Darrell R. Borger, L. Cristina Gavrilescu, Maria C. Bucur, Mircea Ivan, James A. DeCaprio

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

This study was undertaken to interrogate cancer cell survival during long-term hypoxic stress. Two systems with relevance to carcinogenesis were employed: Fully transformed BJ cells and a renal carcinoma cell line (786-0). The dynamic of AMPK activity was consistent with a prosurvival role during chronic hypoxia. This was further supported by the effects of AMPK agonists and antagonists (AICAR and compound C). Expression of a dominant-negative AMPK alpha resulted in a decreased ATP level and significantly compromised survival in hypoxia. Dose-dependent prosurvival effects of rapamycin were consistent with mTOR inhibition being a critical downstream mediator of AMPK in persistent low oxygen.

Original languageEnglish (US)
Pages (from-to)230-234
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume370
Issue number2
DOIs
StatePublished - May 30 2008
Externally publishedYes

Keywords

  • AMPK
  • Apoptosis
  • Cancer
  • Hypoxia
  • Rapamycin
  • mTOR

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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