Heme oxygenase system in ischemia and reperfusion injury.
Ischemia/reperfusion injury (IRI) is a multifactorial antigen-independent process that affects both early and late graft function after transplantation. The complex mechanism of IRI can be attributed to neutrophil accumulation at the site of tissue injury, release of pro-inflammatory mediators such as oxygen free radicals (OFRs), and cytokines, which lead to cellular injury that culminates in the ultimate graft failure. The heme oxygenase-1 (HO-1) system is among the most critical of cytoprotective mechanisms activated during the cellular stress. The cytoprotection often seen in the transplanted organ following local HO-1 overexpression may include several factors, such as: a) antioxidant function, b) maintenance of microcirculation, c) anti-apoptotic function, and d) anti-inflammatory function. The role of enhanced endogenous HO-1 overexpression, and HO-1 downstream mediators (bilirubin, ferritin, CO), which protect against the IRI sequel, remain currently one of the most active areas of investigation. Indeed, HO-1, which functions to amplify multiple intracellular cytoprotective pathways, may serve as a novel therapeutic concept in transplantation to maximize organ donor pool through their safer use despite prolonged periods of cold ischemia.
Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Sei-ichiro
S
Tsuchihashi
Constantino
C
Fondevila
Jerzy W
JW
Kupiec-Weglinski
D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D001664:Biliverdine / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D004790:Enzyme Induction; D005293:Ferritins / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins; D015427:Reperfusion Injury / Q000201:enzymology* / Q000378:metabolism / Q000517:prevention & control
D008565:Membrane Proteins; D006418:Heme; D002248:Carbon Monoxide; D005293:Ferritins; D007501:Iron; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001664:Biliverdine; D001663:Bilirubin