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

Abstract

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.

Lidocaine induces ROCK-dependent membrane blebbing and subsequent cell death in rabbit articular chondrocytes

“…Rho‐associated coiled‐coil forming protein serine/threonine kinase (ROCK), one of the effectors of the small GTPase Rho, is known to be a key regulator of actomyosin contraction through myosin light chain (MLC) phosphorylation . Previous studies showed that the ROCK inhibitor, Y‐27632, inhibits blebbing and subsequent cell death caused by exposure to 1‐butanol, arsenic trioxide and hydrogen sulfide . ROCK‐mediated blebbing has not previously been reported to occur in chondrocytes.…”

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

“…Exposure of Jurkat T cells to 1-5 mM NaHS at pH 6.0-8.0 induced blebbing and apoptosis by activation of the Rho-Rock pathway and cleavage of caspase-3 and poly-ADP ribose polymerase (PARP) (107). In contrast, H 2 S at physiological concentrations (<10 lM) is a positive physiological enhancer of T cell function (166) (Fig.…”

Hydrogen sulfide donor NaHS induces death of alveolar epithelial L2 cells that is associated with cellular shrinkage, transgelin expression and myosin phosphorylation

“…It has been shown that NaHS generates sulfides (H 2 S, S 2-and HS -) efficiently only at acidic pH (Kanno et al, 2013). Therefore, we first mixed equal volumes of 1 M NaHS and 1 M HCl, and then the mixture was added immediately to the medium at final NaHS concentrations of 2-4 mM.…”

“…It has been reported that the human lymphocyte cell line Jurkat undergoes apoptosis when treated with NaHS at concentrations greater than 1 mM (Kanno et al, 2013). Therefore, L2 cells were exposed to NaHS at final concentrations of 2-4 mM for 1 hr.…”