Division of Clinical Chemistry and Laboratory Haematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland.
Int J Mol Sci. 2022 Dec 7;23(24):15450. doi: 10.3390/ijms232415450.
Ischaemia, followed by reperfusion, causes the generation of reactive oxygen species, overproduction of peroxynitrite, activation of matrix metalloproteinases (MMPs), and subsequently the degradation of heart contractile proteins in the cardiomyocytes. Klotho is a membrane-bound or soluble protein that regulates mineral metabolism and has antioxidative activity. This study aimed to examine the influence of Klotho protein on the MMP-mediated degradation of contractile proteins during ischaemia/reperfusion injury (IRI) to the cardiomyocytes. Human cardiac myocytes (HCM) underwent in vitro chemical IRI (with sodium cyanide and deoxyglucose), with or without the administration of recombinant Klotho protein. The expression of MMP genes, the expression and activity of MMP proteins, as well as the level of contractile proteins such as myosin light chain 1 (MLC1) and troponin I (TnI) in HCM were measured. Administration of Klotho protein resulted in a decreased activity of MMP-2 and reduced the release of MLC1 and TnI that followed in cells subjected to IRI. Thus, Klotho protein contributes to the inhibition of MMP-dependent degradation of contractile proteins and prevents injury to the cardiomyocytes during IRI.
缺血后再灌注会导致活性氧的产生、过氧亚硝酸盐的过度产生、基质金属蛋白酶（MMPs）的激活，随后导致心肌细胞中心脏收缩蛋白的降解。Klotho 是一种膜结合或可溶性蛋白，可调节矿物质代谢并具有抗氧化活性。本研究旨在研究 Klotho 蛋白对缺血/再灌注损伤（IRI）期间 MMP 介导的收缩蛋白降解的影响。人心脏肌细胞（HCM）在体外经历化学性 IRI（使用氰化钠和脱氧葡萄糖），同时给予或不给予重组 Klotho 蛋白。测量 HCM 中 MMP 基因的表达、MMP 蛋白的表达和活性，以及肌球蛋白轻链 1（MLC1）和肌钙蛋白 I（TnI）等收缩蛋白的水平。Klotho 蛋白的给药导致 MMP-2 活性降低，并减少了 IRI 后细胞中 MLC1 和 TnI 的释放。因此，Klotho 蛋白有助于抑制 MMP 依赖性收缩蛋白的降解，并防止 IRI 期间心肌细胞损伤。
