H₂S is actual an endogenous signaling gas molecule and involved in a range of cell physiological processes. However, the mechanism of endogenous H₂S regulating autophagy and apoptosis has not been thoroughly investigated. Here, we try to address this issue by using a H₂S probe, (E)-2-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl)-piperazin-1-yl)-styryl)-1, 3, 3-trimethyl-3H-indol-1-ium iodide (CPC), which could react with endogenous H₂S. Herein, we reported that CPC inhibited autophagy and decreased the expression and activity of NF-E2-related factor 2 (Nrf2), then induced cell apoptosis. CPC inhibited autophagy and promoted apoptosis by inhibiting Nrf2 activation, which was H₂S dependent. Furthermore, we found that CPC inhibited Nrf2 nucleus translocation by inhibiting glutathionylation of Kelch-like ECH-associated protein 1 (Keap1) at the Cys434 residue. CPC also inhibited various cancer cell growth, but had no effect on normal cell growth in vitro, and inhibited A549 cancer growth, but did not affect normal angiogenesis in vivo. Therefore, we not only found a new inhibitor of autophagy and Nrf2, but also suggested a novel mechanism that endogenous H₂S could regulate autophagy, apoptosis and Nrf2 activity through regulating glutathionylation of Keap1 at the Cys434 residue.

H ₂ S实际上是一种内源性信号气体分子，并参与一系列细胞生理过程。但是，尚未彻底研究内源性H ₂ S调节自噬和细胞凋亡的机制。在这里，我们尝试使用H ₂ S探针（E）-2-（4-（4-（7-（二乙氨基）-2-oxo-2H-色烯-3-羰基）-哌嗪- 1-yl）-styryl）-1，3，3-trimethyl-3H-indol-1-iodide（CPC）可以与内源性H ₂ S反应。在此，我们报道CPC抑制自噬并降低其表达和NF-E2相关因子2（Nrf2）的活性，然后诱导细胞凋亡。CPC通过抑制Nrf2活化（H _2）抑制自噬并促进细胞凋亡S依赖。此外，我们发现CPC通过抑制Cys434残基上的Kelch样ECH相关蛋白1（Keap1）的谷胱甘肽化来抑制Nrf2核移位。CPC还可以抑制各种癌细胞的生长，但对体外正常细胞的生长没有影响，并且可以抑制A549癌症的生长，但不影响体内的正常血管生成。因此，我们不仅发现了一种新的自噬抑制剂和Nrf2，而且还提出了一种新的机制，即内源性H ₂ S可以通过调节Cys434残基处Keap1的谷胱甘肽酰化来调节自噬，凋亡和Nrf2活性。