Department of Pathophysiology, College of Basic Medicine, Xinjiang Medical University, Urumqi 830000, China.
Laboratory Animal Centre of Xinjiang Medical University, Urumqi 830000, China.
Exp Gerontol. 2023 May;175:112157. doi: 10.1016/j.exger.2023.112157. Epub 2023 Mar 28.
Klotho (KL) is a renal protein with aging-suppression properties that mediates its regulatory effect during cardiac fibroblast aging. However, to determine whether KL can protect aged myocardial cells by attenuating ferroptosis, this study aimed to investigate the protective effect of KL on aged cells and to explore its potential mechanism. Cell injury of H9C2 cells was induced with D-galactose (D-gal) and treated with KL in vitro. This study demonstrated that D-gal induces aging in H9C2 cells. D-gal treatment increased β-GAL(β-galactosidase) activity, decreased cell viability, enhanced oxidative stress, reduced mitochondrial cristae, and decreased the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase-4 (GPx4), and P53, which are primary regulators of ferroptosis. The results showed that KL can eliminate D-gal-induced aging in H9C2 cells, likely due to its ability to increase the expression of the ferroptosis-associated proteins SLC7A11 and GPx4. Moreover, pifithrin-α, a P53-specific inhibitor, enhanced the expression of SLC7A11 and GPx4. These results suggest that KL may be involved in D-gal-induced H9C2 cellular aging during ferroptosis, mainly through the P53/SLC7A11/GPx4 signaling pathway.
Klotho (KL) 是一种具有抗衰老特性的肾脏蛋白，它在心脏成纤维细胞衰老过程中发挥调节作用。然而，为了确定 KL 是否可以通过减轻铁死亡来保护衰老的心肌细胞，本研究旨在探讨 KL 对衰老细胞的保护作用及其潜在机制。本研究在体外使用 D-半乳糖（D-gal）诱导 H9C2 细胞损伤并给予 KL 处理。结果表明，D-gal 诱导 H9C2 细胞衰老。D-gal 处理增加了β-GAL（β-半乳糖苷酶）活性，降低了细胞活力，增强了氧化应激，减少了线粒体嵴，并降低了铁死亡主要调节因子溶质载体家族 7 成员 11（SLC7A11）、谷胱甘肽过氧化物酶 4（GPx4）和 P53 的表达。KL 可以消除 D-gal 诱导的 H9C2 细胞衰老，这可能是由于其增加铁死亡相关蛋白 SLC7A11 和 GPx4 的表达所致。此外，P53 特异性抑制剂 pifithrin-α 增强了 SLC7A11 和 GPx4 的表达。这些结果表明，KL 可能参与了 D-gal 诱导的 H9C2 细胞铁死亡过程中的衰老，主要通过 P53/SLC7A11/GPx4 信号通路。
