Mitogen-activated protein kinases regulate HO-1 gene transcription after ischemia-reperfusion lung injury

Xuchen Zhang, Eric L. Bedard, Richard Potter, Robert Zhong, Jawed Alam, Augustine M.K. Choi, Patty J. Lee

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Lung ischemia-reperfusion (I-R) is an important model of oxidant-mediated acute lung and vascular injury. Heme oxygenase-1 (HO-1) is a cytoprotective gene that is markedly induced by lung I-R injury. HO-1 mRNA is increased in mouse lung after 30 min of lung hilar clamping (ischemia) followed by 2-6 h of unclamping (reperfusion) compared with control mice. In a variety of vascular cell types, HO-1 mRNA is induced after 24 h of anoxia followed by 30 min-1 h of reoxygenation (A-R). Transfection studies reveal that the promoter and 5′-distal enhancer E1 are necessary and sufficient for increased HO-1 gene transcription after A-R. Immunoblotting studies show all three subfamilies of MAPKs (ERK, JNK, and p38) are activated by 15 min of reperfusion. We also demonstrate that HO-1 gene transcription after A-R involves ERK, JNK, and p38 MAPK pathways. Together, our data show that I-R not only induces HO-1 gene expression in mouse lungs and vascular cells but that gene transcription occurs via the promoter and E1 enhancer and involves upstream MAPK pathways.

Original languageEnglish (US)
Pages (from-to)L815-L829
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number4 27-4
DOIs
StatePublished - Oct 2002

Keywords

  • Gene regulation
  • Heme oxygenase
  • Mitogen-activated protein kinases
  • Oxidant injury

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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