Emerging roles of proteasomes in ischemia-reperfusion injury of organs.
Proteasomes are the main non-lysosomal, multicatalytic proteinase complexes involved in the degradation of most intracellular proteins and in numerous cell processes. Studies from isolated cell models indicate that agents that induce oxidative stress may also damage proteasomes. Similarly, continuous oxidative stress during cell aging may impair proteasome activity. In ischemia-reperfusion models of organ injury, proteasomes may be involved in several ways. First, proteasomes were found to be targets of ischemia-reperfusion injury of the brain and heart. Second, proteasome activity increased in liver models of ischemia-reperfusion. Third, proteasome inhibition prevented ischemia-reperfusion injury of the brain, heart and kidney. A major mechanism by which proteasome inhibitors may confer tissue protection is inactivation of transcription activator nuclear factor-kappaB resulting in a block of expression of cytokines and cell adhesion molecules during the reperfusion phase. Thus, proteasome inhibition represents a novel strategy for the treatment of pathologies such as stroke, infarction, and kidney failure.
Kukan
M
M
Laboratory of Perfused Organs, SCOT, Slovak Medical University - Institute of Preventive and Clinical Medicine, Bratislava, Slovakia. kukan@upkm.sk
D000818:Animals; D007511:Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012171:Retinal Vessels
D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex