cardiac protection by preconditioning is generated via an iron-signal created by proteasomal degradation of iron proteins心脏保护的预处理是通过iron-signal由蛋白酶体降解生成的铁蛋白.pdfVIP

Cardiac Protection by Preconditioning Is Generated via an Iron-Signal Created by Proteasomal Degradation of Iron Proteins 1 1 3 2 . Baruch E. Bulvik , Eduard Berenshtein , Esther G. Meyron-Holtz , Abraham M. Konijn * , Mordechai Chevion1. 1 Departments of Cellular Biochemistry and Human Genetics, Faculties of Dental Medicine and Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel, 2 Human Nutrition and Metabolism, Faculties of Dental Medicine and Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel, 3 Laboratory for Molecular Nutrition, Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Technion City, Haifa, Israel Abstract Ischemia associated injury of the myocardium is caused by oxidative damage during reperfusion. Myocardial protection by ischemic preconditioning (IPC) was shown to be mediated by a transient ‘iron-signal’ that leads to the accumulation of apoferritin and sequestration of reactive iron released during the ischemia. Here we identified the source of this ‘iron signal’ and evaluated its role in the mechanisms of cardiac protection by hypoxic preconditioning. Rat hearts were retrogradely perfused and the effect of proteasomal and lysosomal protease inhibitors on ferritin levels were measured. The iron-signal was abolished, ferritin levels were not increased and cardiac protection was diminished by inhibition of the proteasome prior to IPC. Similarly, double amounts of ferritin and better recovery after ex vivo ischemia-and-reperfusion (I/R) were found in hearts from in vivo hypoxia pre-conditioned animals. IPC followed by normoxic perfusion for 30 min (‘delay’) prior to I/R caused a reduced ferritin accumulation at the end