Heme oxygenase-1: unleashing the protective properties of heme.
Heme oxygenase (HO)-1 catabolizes heme into three products: carbon monoxide (CO), biliverdin (which is rapidly converted to bilirubin) and free iron (which leads to the induction of ferritin, an iron-binding protein). HO-1 serves as a "protective" gene by virtue of the anti-inflammatory, anti-apoptotic and anti-proliferative actions of one or more of these three products. Administration of CO, biliverdin, bilirubin or iron-binding compounds is protective in rodent disease models of ischemia-reperfusion injury, allograft and xenograft survival, intimal hyperplasia following balloon injury or as seen in chronic graft rejection and others. We suggest that the products of HO-1 action could be valuable therapeutic agents and speculate that HO-1 functions as a "therapeutic funnel", mediating the beneficial effects attributed to other molecules, such as interleukin-10 (IL-10), inducible nitric oxide synthase (NOS2; iNOS) and prostaglandins. This Review is the third in a series on the regulation of the immune system by metabolic pathways.
Otterbein
Leo E
LE
Division of Pulmonary and Critical Care Medicine, Montifiore University Hospital, University of Pittsburgh School of Medicine, 3459 5th Avenue, Pittsburgh, PA 15213, USA.
Soares
Miguel P
MP
Yamashita
Kenichiro
K
Bach
Fritz H
FH
D000818:Animals; D001663:Bilirubin / Q000276:immunology / Q000378:metabolism; D001664:Biliverdine / Q000276:immunology / Q000378:metabolism; D002248:Carbon Monoxide / Q000276:immunology / Q000378:metabolism; D006418:Heme / Q000276:immunology / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000276:immunology*; D051547:Heme Oxygenase-1; D006801:Humans; D008565:Membrane Proteins; D020011:Protective Agents / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology
D008565:Membrane Proteins; D020011:Protective Agents; D006418:Heme; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001664:Biliverdine; D001663:Bilirubin