Sulfuretted hydrogen ameliorates high dose glucose-induced podocyte apoptosis via orchestrating AMPK/mTOR...

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 (H₂S) 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 H₂S 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 H₂S as well as the accompanying molecular mechanism.

In this study, we found that glucose-induced podocyte apoptosis could be largely rescued by H₂S 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 H₂S 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 H₂S administration in clinical trials.