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二半胱氨酸丙烯醛加合物的形成通过减轻 ROS 和干预细胞凋亡降低丙烯醛的细胞毒性。

Formation of di-cysteine acrolein adduct decreases cytotoxicity of acrolein by ROS alleviation and apoptosis intervention.

机构信息

College of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China.

Department of Food Science and Engineering, Jinan University, Guangzhou 510632, China.

出版信息

J Hazard Mater. 2020 Apr 5;387:121686. doi: 10.1016/j.jhazmat.2019.121686. Epub 2019 Nov 13.

DOI:10.1016/j.jhazmat.2019.121686
PMID:31780296
Abstract

Acrolein (ACR) is a toxic contaminant for humans. Our previous research indicated that l-cysteine (Cys) decreased the cytotoxicity of acrolein possibly via adduct formation, but which adduct contributed to the toxicity-lowering effect remains unknown. In this work, we identified a di-cysteine acrolein adduct (ACR-di-Cys) and investigated its toxicity against human bronchial epithelial cell line HBE and colon cancer cell line Caco-2. ACR-di-Cys tremendously decreased acrolein-induced cytotoxicity via alleviating ROS and apoptosis intervention. In the condition of no presence of free cysteine, however, this adduct can convert to mono-ACR-Cys in PBS solution by losing a molecule of cysteine conjugated at CC bond. ACR-mono-Cys showed much higher toxicity than ACR-di-Cys, and even higher than acrolein after 48 h exposure. This study indicated that cysteine can react with acrolein to form adducts with different acrolein-detoxifying capacity, and a sufficient intake of cysteine or cysteine-containing proteins can maximize the detoxifying effect for acrolein via the formation of a highly detoxifying agent, ACR-di-Cys.

摘要

丙烯醛(ACR)是一种对人类有毒的污染物。我们之前的研究表明,半胱氨酸(Cys)通过加合物形成降低丙烯醛的细胞毒性,但哪种加合物有助于降低毒性仍不清楚。在这项工作中,我们鉴定了一种二半胱氨酸丙烯醛加合物(ACR-二-Cys),并研究了其对人支气管上皮细胞系 HBE 和结肠癌细胞系 Caco-2 的毒性。ACR-二-Cys 通过减轻 ROS 和凋亡干预,极大地降低了丙烯醛诱导的细胞毒性。然而,在没有游离半胱氨酸存在的情况下,该加合物可以通过失去与 CC 键共轭的一个半胱氨酸分子在 PBS 溶液中转化为单-ACR-Cys。ACR-单-Cys 的毒性比 ACR-二-Cys 高得多,暴露 48 小时后甚至比丙烯醛还高。这项研究表明,半胱氨酸可以与丙烯醛反应形成具有不同丙烯醛解毒能力的加合物,通过形成一种高解毒剂 ACR-二-Cys,摄入足够的半胱氨酸或含半胱氨酸的蛋白质可以最大限度地发挥丙烯醛的解毒作用。

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