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Am. J. Respir. Cell Mol. Biol., Volume 27, Number 1, July, 2002 8-16

Heme Oxygenase-1
The "Emerging Molecule" Has Arrived

Danielle Morse and Augustine M. K. Choi

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Organisms on our planet have evolved in an oxidizing environment that is intrinsically inimical to life, and cells have been forced to devise means of protecting themselves. One of the defenses used most widely in nature is the enzyme heme oxygenase-1 (HO-1). This enzyme performs the seemingly lackluster function of catabolizing heme to generate bilirubin, carbon monoxide, and free iron. Remarkably, however, the activity of this enzyme results in profound changes in cells' abilities to protect themselves against oxidative injury. HO-1 has been shown to have anti-inflammatory, antiapoptotic, and antiproliferative effects, and it is now known to have salutary effects in diseases as diverse as atherosclerosis and sepsis. The mechanism by which HO-1 confers its protective effect is as yet poorly understood, but this area of invetsigation is active and rapidly evolving. This review highlights current information on the function of HO-1 and its relevance to specific pulmonary and cardiovascular diseases.

Abbreviations: activator protein-1, AP-1; basic region/leucine zipper, bZIP; cyclic guanosine monophosphate, cGMP; carbon monoxide, CO; extracellular signal-regulated kinase, ERK; hypoxia-inducible factor-1, HIF-1heme oxygenase, HO; interleukin, IL; c-Jun N-terminal kinase, JNK; lipopolysaccharide, LPS; mitogen-activated protein kinase, MAP kinase; nuclear factor, NF; NF-E2-related factor 2, Nrf2; nitric oxide, NO; NO synthase, NOS; reactive oxygen species, ROS; signal transducer and activator of transcription, STAT; stress response element, StRE; tumor necrosis factor-alpha , TNF-alpha .




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