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

Overview

MeSH

  • Animals
  • Aorta
  • Cells, Cultured
  • Enhancer Elements, Genetic
  • Enzyme Inhibitors
  • Flavonoids
  • Heme Oxygenase-1
  • Imidazoles
  • Membrane Proteins
  • Mice
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases
  • Muscle, Smooth, Vascular
  • Mutagenesis
  • Promoter Regions, Genetic
  • Pulmonary Artery
  • Pyridines
  • RNA, Messenger
  • Rats
  • Transcription, Genetic
  • p38 Mitogen-Activated Protein Kinases

MeSH Major

  • Gene Expression Regulation, Enzymologic
  • Heme Oxygenase (Decyclizing)
  • Lung Diseases
  • MAP Kinase Signaling System
  • Reperfusion Injury

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.

publication date

  • October 2002

has subject area

  • Animals
  • Aorta
  • Cells, Cultured
  • Enhancer Elements, Genetic
  • Enzyme Inhibitors
  • Flavonoids
  • Gene Expression Regulation, Enzymologic
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Imidazoles
  • Lung Diseases
  • MAP Kinase Signaling System
  • Membrane Proteins
  • Mice
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases
  • Muscle, Smooth, Vascular
  • Mutagenesis
  • Promoter Regions, Genetic
  • Pulmonary Artery
  • Pyridines
  • RNA, Messenger
  • Rats
  • Reperfusion Injury
  • Transcription, Genetic
  • p38 Mitogen-Activated Protein Kinases

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00485.2001

PubMed ID

  • 12225959

Additional Document Info

start page

  • L815

end page

  • L829

volume

  • 283

number

  • 4