Sulfuretted hydrogen ameliorates high dose glucose-induced podocyte apoptosis via orchestrating AMPK/mTOR cascade-mediated anti-apoptotic effects

• Published in: Annals of translational medicine 2021-10, Vol.9 (20), p.1586-1586
• Main Authors: Huang, Yong, Cheng, Jie, Zhou, Yehua, Zhang, Yanhui, Zhou, Shuhui, Li, Qingzhen, Peng, Lin, Wang, Maohong, Song, Weiguo, Wu, Guoqing
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 2305-5839; 2305-5839
• DOI: 10.21037/atm-21-5152

Podocytes play a pivotal role in the glomerular filtration barrier and contribute to proteinuria and glomerulosclerosis through abnormal apoptosis. Longitudinal studies have indicated the protective properties of hydrogen sulfide (H S) against neuronal cell apoptosis, whereas the biological function and the underlying molecular mechanism on glucose-induced podocyte apoptosis are largely unknown. Herein, we conducted multifaceted biological analyses to verify the potential function of H S in glucose-induced podocyte apoptosis by examining apoptotic proteins and markers (e.g., caspase 3, Hoechst) and antioxidative effects [e.g., reactive oxygen species (ROS), lipid peroxidation, superoxide dismutase (SOD), catalase (CAT)]. Then, we took advantage of transcriptome sequencing and biological analyses to further determine the potential influence of H S as well as the accompanying molecular mechanism. In this study, we found that glucose-induced podocyte apoptosis could be largely rescued by H S via antioxidative responses, which was further confirmed by transcriptome sequencing and bioinformatics analyses. According to apoptotic signaling analysis, the over-activated AMPK/mTOR signaling cascade in glucose-treated podocytes was effectively restrained. For the first time, we indicated the protective effect and mechanism of H S in podocytes by restricting glucose-induced apoptosis and suppressing the abnormally activated AMPK/mTOR signaling cascade. Our findings provide new references for podocyte apoptosis-associated diseases and also indicate the potential of H S administration in clinical trials.