Bovine pulmonary artery endothelial cells (BPAEC) respond in a dose-dependent manner to millimolar (0–10) levels of sodium sulfide (NaHS). No measurable increase in caspase-3 activity and no change in the extent of autophagy (or mitophagy) were observed in BPAEC. However, lactate dehydrogenase levels increased in the BPAEC exposed NaHS, which indicated necrotic cell death. In the case of galactose-conditioned BPAEC, the toxicity of NaHS was increased by 30% compared to that observed in BPAEC maintained in the regular glucose-containing culture medium, which indicated a link between mitochondrial oxidative phosphorylation and the mechanism of toxicant action. This is consistent with the widely held view that cytochrome c oxidase (complex IV of the mitochondrial electron-transport system) is the principal molecular target involved in the acute toxicity of “sulfide” (H₂S/HS^–). In support of this view, elevated NO (which can reverse cytochrome c oxidase inhibition) ameliorated the toxicity of NaHS and, conversely, suppression of endogenous NO production exacerbated the observed toxicity. Respirometric measurements showed the BPAEC to possess a robust sulfide oxidizing system, which was able to out-compete cytochrome c oxidase for available H₂S/HS^– at micromolar concentrations. This detoxification system has previously been reported by other groups in several cell types, but notably, not neurons. The findings appear to provide some insight into the question of why human survivors of H₂S inhalation frequently present at the clinic with respiratory insufficiency/pulmonary edema, while acutely poisoned laboratory animals tend to either succumb to cardiopulmonary paralysis or fully recover without any intervention.

中文翻译：

---

一氧化氮对牛肺动脉内皮细胞的硫化物毒性及其调控

牛肺动脉内皮细胞（BPAEC）对毫摩尔（0-10）的硫化钠（NaHS）水平呈剂量依赖性。在BPAEC中未观察到caspase-3活性的可测量增加，并且自噬（或自噬）的程度也没有变化。但是，暴露于BPAEC的NaHS中乳酸脱氢酶水平升高，这表明坏死细胞死亡。在半乳糖调节的BPAEC情况下，与在常规含葡萄糖培养基中维持的BPAEC相比，NaHS的毒性增加了30％，这表明线粒体氧化磷酸化与毒性作用机理之间存在联系。₂ S / HS ^–）。支持该观点的是，升高的NO（可逆转细胞色素C氧化酶抑制作用）改善了NaHS的毒性，相反，抑制内源性NO的产生加剧了所观察到的毒性。呼吸计测量表明所述BPAEC拥有一个强大的硫化物氧化系统，它能够外竞争细胞色素C氧化酶可用ħ ₂ S / HS ^-在微摩尔浓度。该排毒系统先前已被其他研究小组在几种细胞类型中报告，但值得注意的是神经元。这些发现似乎为为什么人类H ₂幸存者的问题提供了一些见解。吸入经常在临床上出现呼吸功能不全/肺水肿，而急性中毒的实验动物往往会屈服于心肺麻痹或在没有任何干预的情况下完全康复。