Function of hypertrophic growth in cardiocytes to furin belong to the yeast Kex2 endoprotease family

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When cardiocytes undergo the stretch force, they adapt by developing cellular hypertrophic growth and elevated furin. The cells incubated with furin-specific inhibitors were supressed the stretch-induced hypertrophoc growth. Thus, we suggest that furin catalyses the conversion of growth-promoting pro-proteins to their active form, which might induce hypertrophic growth in cardiocytes. Then, we examined growth-promoting peptied transforming growth factor -β(TGF-β) and parathyroid hormone-related protein (PTHrP) including the furin-specific Arg-X-X-Arg (RXXR) motif in myocardium. For study, we used of well-differentiated mouse β-cell line MIN6, and examined function of PTHrP.Early passage contained the high level of insulin, in contrust late passage content the low level of insulin.Furin mRNA were more expressed in late passage than in early passage. Glucosestimulated insulin secretion levels were increased in early passage, but were decresed in late passage. We suggest that the function … More of PTHrP induced further differentiation in well differentiated β-cell, and farther growth in growing β-cell.We believe that PTHrP does not indused growth and differentiation simultaneously in a single β-Cell. PTHrP is co-expressed with furin in stretched myocardium, therefor, furin may be responsible for the conversion of PTHrP proprotain to their active form. We believe that PTHrP active form indeces further growth in hypertrophic myocardium and further contractile force in normal myocardium. We examined whether PTHrP exhibits hypertrpphic growth and contractile force in myocardium. We generated exprimental myocardial infarction (MI) by ligating the left anterior discending coronary artery in rat. We examined TGF-β, PTHrP and furin expression in atrium and ventricles (on day 1 , 3, 7, 14, 28 after MI) by Northern blot. We exmined for immunodetection of TGF-β, PTHrP and furin by Western blot and immunostaining in the ventricular myocardium, including infarction tissue. When hypertrophic growth is induced in neonatal rat cardiocytes by stretching, the cardiocytes express high levels of the proprotein-processing enzyme furin. We believed that the furin-specific inhibitors, dec-Arg-Val-Lys-Arg-CMK and variant a1-antitrypsin with the inhibitory determinant Arg-X-X-Arg, suppressed the stretch-induced hypertrophic growth of cardiocytes.Though we examined these probrems, there were not rising on the suffcient results. At present, the examination will be continuously carried out. Less