The cellular effects of hydrogen sulfide (H₂S) signaling may be partially mediated by the formation of alkyl persulfides from thiols, such as glutathione and protein cysteine residues. Persulfides are potent nucleophiles and reductants and therefore potentially an important endogenous antioxidant or protein post-translational modification. To directly study the cellular effects of persulfides, cysteine trisulfide (Cys-S₃) has been proposed as an in situ persulfide donor, as it reacts with cellular thiols to generate cysteine persulfide (Cys-S-S⁻). Numerous pathways sense and respond to electrophilic cellular stressors to inhibit cellular proliferation and induce apoptosis, however the effect of Cys-S₃ on the cellular stress response has not been addressed. Here we show that Cys-S₃ inhibited cellular metabolism and proliferation and rapidly induced cellular- and ER-stress mechanisms, which were coupled to widespread protein-thiol oxidation. Cys-S₃ reacted with Na₂S to generate cysteine persulfide, which protected human cell lines from ER-stress. However this method of producing cysteine persulfide contains excess sulfide, which interferes with the direct analysis of persulfide donation. We conclude that cysteine trisulfide is a thiol oxidant that induces cellular stress and decreased proliferation.

硫化氢 (H ₂ S) 信号转导的细胞效应可能部分由硫醇（如谷胱甘肽和蛋白质半胱氨酸残基）形成的烷基过硫化物介导。过硫化物是有效的亲核试剂和还原剂，因此可能是一种重要的内源性抗氧化剂或蛋白质翻译后修饰。为了直接研究过硫化物的细胞效应，已提议将半胱氨酸三硫化物 (Cys-S _{3 ) 作为}原位过硫化物供体，因为它与细胞硫醇反应生成半胱氨酸过硫化物 (Cys-SS ^- )。_{许多途径感知和响应亲电细胞应激源以抑制细胞增殖和诱导细胞凋亡，但是 Cys-S 3}的作用关于细胞应激反应的问题尚未得到解决。在这里，我们表明 Cys-S ₃抑制细胞代谢和增殖并迅速诱导细胞和 ER 应激机制，这些机制与广泛的蛋白质-硫醇氧化相结合。Cys-S ₃与Na ₂ S反应生成半胱氨酸过硫化物，保护人类细胞系免受ER应激。然而这种生产半胱氨酸过硫化物的方法含有过量的硫化物，这会干扰直接分析过硫化物的贡献。我们得出结论，半胱氨酸三硫化物是一种硫醇氧化剂，可诱导细胞应激并减少增殖。