Department of Ophthalmology and Vision Science, Eye and Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, China.
Dis Markers. 2021 Nov 11;2021:1602797. doi: 10.1155/2021/1602797. eCollection 2021.
Retinitis pigmentosa (RP) is a major cause of blindness that is difficult to diagnose and treat. PKM2, a subtype of pyruvate kinase, is strongly associated with oxidative stress and is expressed in photoreceptors. We investigated whether PKM2 reduces photoreceptor cell apoptosis and evaluated possible antiapoptotic mechanisms in RP. We established RP models by exposing 661W cells to blue light and modulated PKM2 activity using a PKM2 inhibitor. We measured the apoptosis rates using calcein-acetoxymethyl ester/propidium iodide double staining and Cell Counting Kit-8, the oxidative stress levels using a reactive oxygen species assay, and the changes in protein expression by western blotting. Photodamage increased PKM2 expression, cellular oxidative stress, and apoptosis of 661W cells. PKM2 inhibition significantly reduced the levels of apoptosis and oxidative stress induced by photodamage. Our data suggest that PKM2 is a potential disease marker and therapeutic target for RP.
色素性视网膜炎(RP)是一种难以诊断和治疗的主要致盲原因。丙酮酸激酶(PKM)亚型 2 与氧化应激强烈相关,并在光感受器中表达。我们研究了 PKM2 是否能减少光感受器细胞凋亡,并评估了 RP 中的可能抗凋亡机制。我们通过用蓝光照射 661W 细胞建立了 RP 模型,并使用 PKM2 抑制剂调节 PKM2 活性。我们使用 calcein-acetoxymethyl ester/propidium iodide 双重染色和 Cell Counting Kit-8 测量细胞凋亡率,使用活性氧测定法测量氧化应激水平,并通过 Western blot 测量蛋白表达的变化。光损伤增加了 661W 细胞中 PKM2 的表达、细胞氧化应激和凋亡。PKM2 抑制显著降低了光损伤诱导的细胞凋亡和氧化应激水平。我们的数据表明,PKM2 是 RP 的潜在疾病标志物和治疗靶点。