Heart HIF-1α and MAP kinases during hypoxia: Are they associated in vivo?

Anna Caretti, Sandrine Morel, Giuseppina Milano, Monica Fantacci, Paola Bianciardi, Raffaella Ronchi, Giuseppe Vassalli, Ludwig K. Von Segesser, Michele Samaja

Research output: Contribution to journalArticlepeer-review

Abstract

To study the in vivo dynamics of hypoxia-inducible factor 1α (HIF-1α), master regulator of O2-dependent gene expression, and mitogen-activated protein kinases (MAPKs) in the hypoxic myocardium, Sprague-Dawley rats (n = 4 to 6 per group) were exposed to 1-hr hypoxia (10% O2), 23-hr hypoxia, and 23-hr hypoxia, followed by reoxygenation. HIF-1a increased 15-fold after 1-hr hypoxia, remained constant for 23 hrs, and returned to baseline on reoxygenation. Extracellular signal-regulated kinases (ERK1/2) were unchanged throughout. Phosphorylated p38 increased 4-fold after 1-hr hypoxia and returned to baseline within 23-hr hypoxia. The activity of stress-activated protein kinases/c-Jun NH2-terminal kinases (JNKs), measured as phosphorylated c-Jun, increased 3-fold after 1-hr hypoxia and remained sustained afterward. Furthermore, HIF-1α was halved in rats that were administered with the p38 inhibitor SB202190 and made hypoxic for 1 hr. In conclusion, although very sensitive to the reoxygenation, HIF-1α is overexpressed in vivo in the hypoxic myocardium, and its acute induction by hypoxia is correlated with that of p38.

Original languageEnglish
Pages (from-to)887-894
Number of pages8
JournalExperimental Biology and Medicine
Volume232
Issue number7
Publication statusPublished - Jul 2007

Keywords

  • c-Jun
  • ERK1/2
  • HSP27
  • JNK
  • p38
  • SB202190

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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