A novel strategy against ischemia and reperfusion injury: cytoprotection with heme oxygenase system.
Much interest has recently been focused on the physiological/pathological role of the heme oxygenase (HO) system, the rate-limiting step in the conversion of heme, in inflammatory events. The HO system may be instrumental in mediating a number of cytoprotective effects, because of its end products, biliverdin, carbon monoxide (CO) and ferrous free iron (Fe2+). As each of the byproducts acts dependently and/or co-operatively with each other, their in vivo effects are complex. In general, the HO system is thought to exert three major functions in ischemia/reperfusion injury: (1) anti-oxidant effects; (2) maintenance of microcirculation; and (3) modulatory effects upon the cell cycle. The anti-oxidant functions depend on heme degradation, oxygen consumption and the production of biliverdin/ferritin via iron accumulation. On the other hand, the production of CO, which has vasodilatory and anti-platelet aggregative properties, can maintain tissue microcirculation. Strikingly, CO may also be instrumental in anti-apoptotic and cell arrest mechanisms. The HO system prevents early injury in the re-perfused organ, and inhibits the function of immune reactive cells, such as neutrophils, macrophages and lymphocytes. The role of the HO system as a novel strategy to mitigate an antigen-independent ischemia/reperfusion injury has been documented in a number of transplantation models.
Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Los Angeles, CA 90095, USA.
Masamichi
M
Katori
Dean M
DM
Anselmo
Ronald W
RW
Busuttil
Jerzy W
JW
Kupiec-Weglinski
D000818:Animals; D001664:Biliverdine / Q000502:physiology; D002248:Carbon Monoxide / Q000502:physiology; D019610:Cytoprotection / Q000502:physiology*; D004790:Enzyme Induction; D005609:Free Radicals; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D051547:Heme Oxygenase-1; D006801:Humans; D007501:Iron / Q000378:metabolism; D007511:Ischemia / Q000517:prevention & control*; D008565:Membrane Proteins; D010100:Oxygen / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*
D005609:Free Radicals; D008565:Membrane Proteins; D006418:Heme; D002248:Carbon Monoxide; D007501:Iron; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001664:Biliverdine; D010100:Oxygen