Kuo T H, Giacomelli F, Wiener J
Exp Mol Pathol. 1984 Jun;40(3):280-7. doi: 10.1016/0014-4800(84)90045-5.
The role of cardiac lysosomal and nonlysosomal protease alterations in the development of the cardiomyopathy that occurs in genetically diabetic C57BL/KsJ db/db mice has been examined. The db/db mice and age-matched controls were sacrificed between 7 and 24 weeks of age. Cathepsin D activity, myofibrillar alkaline protease (MAP) activity (including serine protease activity), and Ca2+-activated protease activity were determined by using [3H]acetyl-casein as substrate. There is a significant decrease in cathepsin D, MAP, and serine protease activities in the myocardium of 7- to 20-week old diabetic mice with a rebound of these activities toward normal levels by 24 weeks of age. Cathepsin D and MAP activities are inversely related to heart weight in diabetic mice with the higher levels being recorded in association with the most pronounced decrease in heart weight. In contrast, Ca2+-activated protease activity in the hearts of diabetic mice does not differ significantly from controls throughout the period of observation. The results suggest that both lysosomal cathepsin D and nonlysosomal MAP may mediate the accelerated cardiac muscle degradation that occurs in the late stage of diabetic cardiomyopathy in the db/db mice.
研究了心脏溶酶体和非溶酶体蛋白酶改变在遗传性糖尿病C57BL/KsJ db/db小鼠发生的心肌病发展过程中的作用。在7至24周龄期间处死db/db小鼠和年龄匹配的对照小鼠。以[3H]乙酰酪蛋白为底物测定组织蛋白酶D活性、肌原纤维碱性蛋白酶（MAP）活性（包括丝氨酸蛋白酶活性）和Ca2+激活的蛋白酶活性。7至20周龄糖尿病小鼠心肌中的组织蛋白酶D、MAP和丝氨酸蛋白酶活性显著降低，到24周龄时这些活性反弹至正常水平。在糖尿病小鼠中，组织蛋白酶D和MAP活性与心脏重量呈负相关，心脏重量下降最明显时记录到的活性水平较高。相比之下，在整个观察期间，糖尿病小鼠心脏中的Ca2+激活的蛋白酶活性与对照无显著差异。结果表明，溶酶体组织蛋白酶D和非溶酶体MAP都可能介导db/db小鼠糖尿病心肌病晚期发生的加速心肌降解。
