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

Abstract

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 BeSO 4 .Additionally, 16HBE cells were subjected to pretreatment with either a 300 μM dose of sodium hydrosulfide (a hydrogen sulfide donor) or 10 mM DLpropargylglycine (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.

Hydrogen sulfide alleviates beryllium sulfate‐induced ferroptosis and ferritinophagy in 16HBE cells

“…For example, Yoshida et al (2019) reported that cigarette smoke exposure can be mediated by NCOA4, while ferritinophagy promotes unstable iron accumulation, lipid peroxidation, and ferroptosis in human bronchial epithelial cells, which participates in COPDs. In fact, we observed increased intracellular free H 2 S is a third endogenous signaling molecule, which contributes to physiological and pathological responses of various organs through antioxidant defense, anti-inflammation, antiautophagy, and inhibiting ferroptosis (Citi et al, 2018;Jin et al, 2020;Y. P. Liu, Yuan, et al, 2022;Wang et al, 2021).…”

“…However, the role of ferroptosis and ferritinophagy in beryllium disease remains unclear. Intriguingly, our previous results found that BeSO 4 induced oxidative damage, apoptosis, and autophagy in 16HBE cells (Y. P. Liu, Yuan, et al, 2022), as well as PTGS2, a biomarker of ferroptosis was upregulated in 16HBE cells treated with 150 μM BeSO 4 (Yi et al, 2021). In this study, we determine the effect of BeSO 4 on the occurrence of ferroptosis in 16HBE cells with or without the intervention of DFO (a specific inhibitor of ferroptosis) and then preliminarily explored its mechanism (Miao et al, 2022;J.…”

“…Human bronchial epithelial cells (16HBE) were kindly provided by Peking University Health Science Center. Cells were cultured in Dulbecco's modified Eagle's medium (DMEM, Solarbio, China) containing 10% fetal bovine serum (FBS, Gibco, Grand Island, USA) and 1% penicillin/ streptomycin (Biosharp, China) in an incubator at 5% CO 2 and 37 C. The 16HBE cells were pretreated with 50 μM DFO, 300 μM NaHS, or 20 μM NCOA4 siRNA for 6 h and cotreated with 150 μM BeSO 4 for 48 h (Y. P. Liu, Yuan, et al, 2022;Wen et al, 2013;Yi et al, 2021).…”

“…Our research group has previously studied the role of H 2 S in respiratory system and found that H 2 S has various functions such as antioxidant, antiapoptosis, and antiautophagy. However, the effect of H 2 S on ferroptosis and ferritinophagy in 16HBE cells is unknown (Y. P. Liu, Yuan, et al, 2022).…”

Serum‐derived exosomes from SD rats induce inflammation in macrophages through the mTOR pathway

“…A cohort study of workers at seven beryllium processing plants showed that workers exposed to ≥10 μg/m 3 (0.001 μmol/L) beryllium had higher rates of lung cancer, urinary tract cancer, COPD, and cor pulmonale than workers with lower exposures (Schubauer‐Berigan et al, 2011). Many in vitro and in vivo studies have found that beryllium exposure induces inflammation, oxidative stress, apoptosis, and autophagy (Liu et al, 2021; Yi et al, 2020). Beryllium has been shown to interfere with cell homeostasis, generate excessive reactive oxygen species (ROS), and induce mitochondrial dysfunction, leading to pulmonary disease (Ding et al, 2000).…”