Schulz Richard
Cardiovascular Research Group, Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
Annu Rev Pharmacol Toxicol. 2007;47:211-42. doi: 10.1146/annurev.pharmtox.47.120505.105230.
A new paradigm of matrix metalloproteinase-2 (MMP-2) action in the heart undergoing oxidative stress has emerged. Although best known for its role in the proteolysis of extracellular protein targets, MMP-2 is also localized to the sarcomere within the cardiomyocyte. Oxidative stress activates full-length MMP-2 without need for proteolytic processing and inactivates an endogenous inhibitor, tissue inhibitor of metalloproteinase-4. MMP-2 proteolyzes specific targets within the cell to cause acute, reversible contractile dysfunction. Inhibitors of MMPs are discussed and their possible use for the therapy of acute heart injury caused by oxidative stress is examined.
在经历氧化应激的心脏中，基质金属蛋白酶-2（MMP-2）作用的一种新范式已经出现。尽管MMP-2最出名的是其在细胞外蛋白质靶点蛋白水解中的作用，但它也定位于心肌细胞内的肌节。氧化应激无需蛋白水解加工即可激活全长MMP-2，并使一种内源性抑制剂金属蛋白酶组织抑制剂-4失活。MMP-2对细胞内的特定靶点进行蛋白水解，导致急性、可逆的收缩功能障碍。文中讨论了MMP抑制剂，并研究了它们在治疗由氧化应激引起的急性心脏损伤方面的可能用途。
