Pollack Jay R, Witt Richard C, Sugimoto Jeffrey T
Department of Surgery, Creighton University School of Medicine, Omaha, NE 68131, USA.
Mol Cell Biochem. 2003 Sep;251(1-2):47-50.
Two inhibitors of the calcium-dependent cysteine protease, calpain, have markedly different effects on the extent of hypertrophy induced by the alpha-adrenergic agonist, phenylephrine, of cultured neonatal rat ventricular myocytes. E64c, an inhibitor of calpain and other cysteine proteases, stimulated the hypertrophy by 59%. PD 150606, a specific calpain inhibitor, reduced the hypertrophy by 38%. Phenylephrine decreased the proteolysis of a calpain substrate by the cells 1-2 h after its addition but not at 24 h. PD 150606 inhibited proteolytic activity at all times, and the combination of phenylephrine and PD 150606 did not give greater inhibition. This suggests that cysteine proteases of the papain sub-family are involved with the hypertrophic response at two points, promoting hypertrophy at the first and limiting it at the second. Calpain appears to be the protease involved at the first point, and there may be another cysteine protease acting at the second site.
钙依赖性半胱氨酸蛋白酶（钙蛋白酶）的两种抑制剂，对培养的新生大鼠心室肌细胞由α-肾上腺素能激动剂去氧肾上腺素诱导的肥大程度具有明显不同的影响。E64c是一种钙蛋白酶和其他半胱氨酸蛋白酶的抑制剂，可使肥大增加59%。PD 150606是一种特异性钙蛋白酶抑制剂，可使肥大减少38%。去氧肾上腺素在添加后1-2小时可降低细胞对钙蛋白酶底物的蛋白水解作用，但在24小时时则无此作用。PD 150606在所有时间均抑制蛋白水解活性，去氧肾上腺素与PD 150606联合使用并未产生更大的抑制作用。这表明木瓜蛋白酶亚家族的半胱氨酸蛋白酶在两个方面参与了肥大反应，在第一个方面促进肥大，在第二个方面限制肥大。钙蛋白酶似乎是参与第一个方面的蛋白酶，可能存在另一种半胱氨酸蛋白酶作用于第二个位点。
