Cui Xiaomeng, Li Chengjun, He Shuixiang, Li Yarui
Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shannxi, China.
Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Sci Rep. 2025 Jul 2;15(1):23129. doi: 10.1038/s41598-025-04924-2.
HS signal transduction involves various physiological processes, including promoting vasodilation, regulating lipid metabolism, inducing angiogenesis, improving oxidative stress and inflammatory response, and avoiding cell apoptosis. Oxidative stress is an important mechanism that causes the pathological progression of NAFLD. However, the effect and specific mechanism of exogenous HS on oxidative stress in NAFLD are still unclear. Here, we investigated the specific regulatory mechanism of exogenous HS on oxidative stress and inflammation induced by LM in HepG2 cells. HepG2 cells were stimulated with LM with or without GYY4137 (200 µM) treatment for 24 h. The levels of MDA, SOD, ROS, TNF-α, IL-6, and antioxidant related proteins of cells were detected. We found exogenous HS remarkably reduced the levels of MDA, ROS, TNF-α and IL-6 and elevated SOD contents as well as the expression of antioxidant-related proteins in LM-induced HepG2 cells. Moreover, exogenous HS improved the expression of USP22 protein in LM-induced HepG2 cells and inhibited the ubiquitination degradation of SIRT1 through USP22. After USP22 was knocked down, the efficacy of exogenous HS on mitigating LM-induced oxidative damage and inflammatory reaction in HepG2 cells had been weakened. In conclusion, exogenous HS inhibited SIRT1 ubiquitination degradation through USP22, thereby alleviating LM-induced oxidative stress and inflammatory responses in HepG2 cells.
硫化氢信号转导涉及多种生理过程，包括促进血管舒张、调节脂质代谢、诱导血管生成、改善氧化应激和炎症反应以及避免细胞凋亡。氧化应激是导致非酒精性脂肪性肝病病理进展的重要机制。然而，外源性硫化氢对非酒精性脂肪性肝病氧化应激的作用及具体机制仍不清楚。在此，我们研究了外源性硫化氢对肝G2细胞中脂多糖诱导的氧化应激和炎症的具体调控机制。用或不用GYY4137（200μM）处理脂多糖刺激肝G2细胞24小时。检测细胞中丙二醛、超氧化物歧化酶、活性氧、肿瘤坏死因子-α、白细胞介素-6水平以及抗氧化相关蛋白。我们发现外源性硫化氢显著降低脂多糖诱导的肝G2细胞中丙二醛、活性氧、肿瘤坏死因子-α和白细胞介素-6水平，提高超氧化物歧化酶含量以及抗氧化相关蛋白的表达。此外，外源性硫化氢提高脂多糖诱导的肝G2细胞中泛素特异性蛋白酶22蛋白的表达，并通过泛素特异性蛋白酶22抑制沉默信息调节因子1的泛素化降解。在敲低泛素特异性蛋白酶22后，外源性硫化氢减轻脂多糖诱导的肝G2细胞氧化损伤和炎症反应的功效减弱。总之，外源性硫化氢通过泛素特异性蛋白酶22抑制沉默信息调节因子1的泛素化降解，从而减轻脂多糖诱导的肝G2细胞氧化应激和炎症反应。
