Sulfide induces apoptosis and Rho kinase-dependent cell blebbing in Jurkat cells

Hydrogen sulfide (H2S) is a toxic gaseous substance, and accidental exposure to high concentrations of H2S has been reported to be lethal to humans. Inhaled and absorbed H2S is partially dissolved within the circulation and causes toxic effects on lymphocytes. However, the mechanisms involved in H2S toxicity have not been well documented. In this study, we examined the cellular uptake and injury of sulfide-exposed human T lymphocytes (Jurkat). Cells were exposed to a H2S donor, sodium hydroxysulfide (NaHS), at pH 6.0, 7.0, or 8.0 for 1 h at 37 °C in a sealed conical tube to avoid the loss of dissolved H2S gas. Cytotoxicity and cellular sulfide concentrations increased dramatically as the pH of the NaHS solution decreased. Sulfide enhanced the cleavage of caspase-3 and poly (ADP-ribose) polymerase and induced early cellular apoptosis. A pan-caspase inhibitor reduced sulfide-induced apoptosis. These results indicate that sulfide induces pH-dependent and caspase-dependent apoptosis. We also found that blebbing of the plasma membrane occurred in sulfide-exposed cells. Both ROCK-1 and ROCK-2 (Rho kinases) were activated by sulfide, and sulfide-induced cell blebbing was suppressed by a ROCK inhibitor, suggesting that a Rho pathway is involved in sulfide-induced blebbing in lymphocytes.