Hydrogen sulfide alleviates apoptosis and autophagy induced by beryllium sulfate in 16HBE cells

• Published in: Journal of applied toxicology Vol. 42; no. 2; pp. 230 - 243
• Main Authors: Liu, Yan‐ping, Yuan, Xiao‐yan, Li, Xun‐ya, Wang, Ye, Sun, Zhan‐bing, Deng, Wei‐hua, Lei, Yuan‐di, Huang, Lian, Jiang, Tian‐yi, Zhang, Zhao‐hui
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.02.2022
• Subjects: 1-Phosphatidylinositol 3-kinase; 16HBE cell; AKT protein; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Berylliosis; Beryllium; Beryllium - toxicity; Beryllium compounds; beryllium sulfate; Bronchi; Cell cycle; Cell Line; Cell viability; Epithelial Cells; Humans; Hydrogen; Hydrogen sulfide; Hydrogen Sulfide - pharmacology; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Membrane potential; Mitochondria; Pretreatment; Protective Agents - pharmacology; Signal transduction; Signaling; Sodium; Sulfates; TOR protein; Toxicants; 16HBE cell; apoptosis; autophagy; hydrogen sulfide; beryllium sulfate
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4205

Beryllium and its compounds are systemic toxicants that are widely applied in many industries. Hydrogen sulfide has been found to protect cells. The present study aimed to determine the protective mechanisms involved in hydrogen sulfide treatment of 16HBE cells following beryllium sulfate‐induced injury. 16HBE cells were treated with beryllium sulfate doses ranging between 0 and 300 μM BeSO4. Additionally, 16HBE cells were subjected to pretreatment with either a 300 μM dose of sodium hydrosulfide (a hydrogen sulfide donor) or 10 mM DL‐propargylglycine (a cystathionine‐γ‐lyase inhibitor) for 6 hr before then being treated with 150 μM beryllium sulfate for 48 hr. This study illustrates that beryllium sulfate induces a reduction in cell viability, increases lactate dehydrogenase (LDH) release, and increases cellular apoptosis and autophagy in 16HBE cells. Interestingly, pretreating 16HBE cells with sodium hydrosulfide significantly reduced the beryllium sulfate‐induced apoptosis and autophagy. Moreover, it increased the mitochondrial membrane potential and alleviated the G2/M‐phase cell cycle arrest. However, pretreatment with 10 mM DL‐propargylglycine promoted the opposite effects. PI3K/Akt/mTOR and Nrf2/ARE signaling pathways are also activated following pretreatment with sodium hydrosulfide. These results indicate the protection provided by hydrogen sulfide in 16HBE cells against beryllium sulfate‐induced injury is associated with the inhibition of apoptosis and autophagy through the activation of the PI3K/Akt/mTOR and Nrf2/ARE signaling pathways. Therefore, hydrogen sulfide has the potential to be a promising candidate in the treatment against beryllium disease. BeSO4 could reduce cell viability, increase LDH release, and induce cellular apoptosis and autophagy in 16HBE cells. Pretreatment of NaHS could increase the mitochondrial membrane potential and alleviate the G2/M‐phase cell cycle arrest. The protective effects of H2S in 16HBE cells against BeSO4‐induced injury is associated with the inhibition of apoptosis and autophagy through the activation of the PI3K/Akt/mTOR and Nrf2/ARE signaling pathways.