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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, X; Bedard, EL; Potter, R; Zhong, R; Alam, J; Choi, AMK; Lee, PJ

Published Date

  • October 2002

Published In

Volume / Issue

  • 283 / 4

Start / End Page

  • L815 - L829

PubMed ID

  • 12225959

International Standard Serial Number (ISSN)

  • 1040-0605

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00485.2001

Language

  • eng

Conference Location

  • United States