Sulfide induces apoptosis and Rho kinase-dependent cell blebbing in Jurkat cells
Sulfide induces apoptosis and Rho kinase-dependent cell blebbing in Jurkat cells
复制标题
DOI：
10.1007/s00204-013-1027-3
复制
发表时间：
2013-07-01
影响因子：
6.1
通讯作者：
Mukai, Toshiji
中科院分区：
文献类型：
--
作者：
Kanno, Sanae;Hirano, Seishiro;Mukai, Toshiji
硫化氢（H2S）是一种有毒的气体物质，据报道，意外暴露于高浓度的H2S对人类是致命的。吸入和吸收的H2S在循环中部分溶解，并对淋巴细胞产生毒性作用。然而，参与H2S毒性的机制尚未得到很好的记录。在这项研究中，我们研究了硫化物暴露的人T淋巴细胞（Jurkat）的细胞摄取和损伤。在密封的锥形管中，将细胞暴露于pH 6.0、7.0或8.0的H2S供体，羟基硫化钠（NaHS），在37 A ° C下持续1小时，以避免溶解的H2S气体的损失。随着NaHS溶液pH值的降低，细胞毒性和细胞硫化物浓度急剧增加。硫化物可增强caspase-3和聚ADP-核糖聚合酶的裂解，诱导早期细胞凋亡。泛半胱天冬酶抑制剂减少硫化物诱导的细胞凋亡。这些结果表明，硫化物诱导pH依赖性和半胱天冬酶依赖性细胞凋亡。我们还发现，起泡的质膜发生在硫化物暴露的细胞。ROCK-1和ROCK-2（Rho激酶）都被硫化物激活，并且硫化物诱导的细胞起泡被ROCK抑制剂抑制，这表明Rho通路参与了淋巴细胞中硫化物诱导的起泡。
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 A degrees 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.