Excessive hydrogen sulfide causes lung and brain tissue damage by promoting PARP1/Bax and C9 and inhibiting LAMB1.

Excessive hydrogen sulfide (H2S) causes serious damage to human organs and tissues. In this study, we aimed to explore the role and underlying mechanism of excessive H2S in brain and lung tissues. A H2S concentration of 100-800 pm promotes apoptosis and inflammation of brain and lung cells in ICR mice. Mechanistically, a H2S 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 H2S 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 H2S 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 H2S concentration was confirmed using mass spectrometry and western blotting in vivo and in vitro. Combined with in vitro experiments, we found that an excessive H2S concentration promotes the expression of STAT1 and EGFR in HT22 and MML1 cells by inhibiting the expression of LAMB1. In summary, 100-800 pm H2S causes the brain and lung tissue damage in ICR mice, the underlying mechanisms include H2S induced apoptosis and inflammation of mouse brain and lung cells by upregulation of PARP1/Bax and C9, respectively, and H2S might induce fibrosis of mouse brain and lung cells by downregulation of LAMB1.