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Prostacyclin Analog-Suppressed Ischemia–Reperfusion Injury of the Rat Liver: Evaluation by Calpain μ Activation

1997; Elsevier BV; Volume: 73; Issue: 2 Linguagem: Inglês

10.1006/jsre.1997.5200

1095-8673

Meng Wang, Masato Sakon, Hideyuki Miyoshi, Koji Umeshita, Shinichi Kishimoto, Kazunori Taniguchi, Mitsukazu Gotoh, Shinobu Imajoh-Ohmi, Morito Monden,

Heat shock proteins research

Abstract Prostaglandin I 2 has a protective effect on hepatic ischemia–reperfusion injury. However, the exact intracellular mechanisms of this effect have not been elucidated. Calpain μ, a Ca 2+ -dependent protease, has been found to play a role in the ischemia–reperfusion injury of various organs. The hilar area of the left lateral and median lobes of rat livers was clamped for 60 min. A prostaglandin I 2 analog (OP2507, C 35 H 41 NO 4 ) was intravenously administered at 0.1, 0.32, or 1.0 μg/kg/min from 20 min before the ischemia. In addition to biochemical and microscopic analyses, the activation of calpain μ was investigated using specific antibodies against the intermediate (activated) and preactivated forms of calpain μ. The degradation of talin was also studied by Western blotting. When OP2507 was infused at 0.32 and 1.0 μg/kg/min, bile flow significantly increased after reperfusion compared with the control group, consistent with the decrease in serum transaminase levels. Membrane bleb formation and the appearance of the intermediate form of calpain μ were observed at 60 min of ischemia in the control and OP2507 (0.1 μg/kg/min) groups and remained present until 120 min after reperfusion. OP2507 (1.0 μg/kg/min) markedly suppressed not only membrane bleb formation but also calpain μ activation and the degradation of talin. In conclusion, OP2507 suppresses ischemia–reperfusion injury of the rat liver, and its cytoprotective effect is closely associated with the inhibition of calpain μ activation.