Parkinson’s disease is characterized by dopamine dyshomeostasis and oxidative stress. The aldehyde metabolite of dopamine, 3,4-dihydroxyphenylacetaldehyde (DOPAL), has been reported to be cytotoxic and capable of protein modification. Protein modification by DOPAL has been implicated in the pathogenesis of Parkinson’s disease, but the complete pathology is unknown. Our findings show that DOPAL modifies glutathione S-transferase (GST), an important enzyme in the antioxidant defense system. DOPAL, dopamine, and the metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), inhibited the activity of GST isolated from N27 dopaminergic cells at an IC₅₀ of 31.46 μM, 82.32 μM, and 260.0 μM, respectively. DOPAL, dopamine, and DOPAC inhibited commercially available equine liver GST at an IC₅₀ of 23.72 μM, 32.17 μM, and 73.70 μM, respectively. This inhibition was time dependent and irreversible. 1 mM ʟ-cysteine or glutathione fully protected GST activity from DOPAL, DA, and DOPAC inhibition. 1 mM carnosine partially protected GST activity from DA inhibition. Furthermore, ʟ-cysteine was found to protect GST by forming a putative thiazolidine conjugate with DOPAL. We conclude that GST inactivation may be a part of the broader etiopathology of Parkinson’s disease.

帕金森病的特征是多巴胺稳态失调和氧化应激。据报道，多巴胺的醛代谢物 3,4-二羟基苯乙醛 (DOPAL) 具有细胞毒性并能够修饰蛋白质。DOPAL 对蛋白质的修饰与帕金森病的发病机制有关，但完整的病理学尚不清楚。我们的研究结果表明，DOPAL 修饰谷胱甘肽 S-转移酶 (GST)，这是抗氧化防御系统中的一种重要酶。DOPAL、多巴胺和代谢物 3,4-二羟基苯乙酸 (DOPAC) 抑制从 N27 多巴胺能细胞中分离的 GST 的活性，IC ₅₀分别为 31.46 μM、82.32 μM 和 260.0 μM。_{DOPAL、多巴胺和 DOPAC 以 IC 50}抑制市售马肝 GST分别为 23.72 μM、32.17 μM 和 73.70 μM。这种抑制是时间依赖性的并且是不可逆的。1 mM ʟ-半胱氨酸或谷胱甘肽完全保护 GST 活性免受 DOPAL、DA 和 DOPAC 抑制。1 mM 肌肽部分保护 GST 活性免受 DA 抑制。此外，发现 ʟ-半胱氨酸通过与 DOPAL 形成推定的噻唑烷缀合物来保护 GST。我们得出结论，GST 失活可能是帕金森病更广泛病因病理学的一部分。