Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice PRC, Shanghai, 200063, People's Republic of China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, People's Republic of China.
Apoptosis. 2022 Feb;27(1-2):149-160. doi: 10.1007/s10495-021-01705-w. Epub 2022 Feb 4.
Excessive hydrogen sulfide (HS) causes serious damage to human organs and tissues. In this study, we aimed to explore the role and underlying mechanism of excessive HS in brain and lung tissues. A HS concentration of 100-800 pm promotes apoptosis and inflammation of brain and lung cells in ICR mice. Mechanistically, a HS concentration of 100-800 pm upregulates PARP1 and Bax expression in a dose-dependent manner in vivo and in vitro, and functional gain-and-loss experiments verified that an excessive amount of HS plays a pro-apoptotic role in HT22 and MML1 cells via regulation of PARP1 and Bax in vitro. By combining animal and cell experiments, we clarified that excess HS promotes the inflammatory response of mouse brain and lung cells by promoting the expression of C9. In addition, the downregulation of LAMB1 by an excessive HS concentration was confirmed using mass spectrometry and western blotting in vivo and in vitro. Combined with in vitro experiments, we found that an excessive HS concentration promotes the expression of STAT1 and EGFR in HT22 and MML1 cells by inhibiting the expression of LAMB1. In summary, 100-800 pm HS causes the brain and lung tissue damage in ICR mice, the underlying mechanisms include HS induced apoptosis and inflammation of mouse brain and lung cells by upregulation of PARP1/Bax and C9, respectively, and HS might induce fibrosis of mouse brain and lung cells by downregulation of LAMB1.
过量的硫化氢 (HS) 会对人体器官和组织造成严重损害。在本研究中，我们旨在探索过量 HS 在脑和肺组织中的作用及其潜在机制。HS 浓度为 100-800 pm 可促进 ICR 小鼠脑和肺细胞的凋亡和炎症。在体内和体外，机制研究表明，HS 浓度为 100-800 pm 以剂量依赖的方式上调 PARP1 和 Bax 的表达，功能获得和损失实验验证了过量的 HS 通过调节 PARP1 和 Bax 在体外对 HT22 和 MML1 细胞具有促凋亡作用。通过结合动物和细胞实验，我们阐明了过量的 HS 通过促进 C9 的表达来促进小鼠脑和肺细胞的炎症反应。此外，体内和体外实验均证实过量 HS 浓度可下调 LAMB1 的表达。结合体外实验，我们发现过量的 HS 通过抑制 LAMB1 的表达，促进 HT22 和 MML1 细胞中 STAT1 和 EGFR 的表达。总之，100-800 pm 的 HS 导致 ICR 小鼠的脑和肺组织损伤，其潜在机制包括 HS 通过上调 PARP1/Bax 和 C9 分别诱导小鼠脑和肺细胞的凋亡和炎症，以及 HS 通过下调 LAMB1 诱导小鼠脑和肺细胞的纤维化。
