Ham Yat-Hing, Jason Chan K K, Chan Wan
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Chem Res Toxicol. 2020 Jul 20;33(7):1815-1821. doi: 10.1021/acs.chemrestox.0c00055. Epub 2020 Apr 30.
Oxidative stress is associated with the pathophysiology of many degenerative human diseases, including Alzheimer's disease, atherosclerosis, Parkinson's disease, and cancers. We discovered in our previous study that thioproline (SPro), a proline analogue, is generated in oxidant-exposed cells. With the prior observation that SPro served as an efficient nitrile trapping agent, we tested in this study the hypothesis that this oxidative stress generated cysteine-formaldehyde adduct, SPro, may serve as an antioxidant protecting cells from oxidative stress. Interestingly, results showed that HeLa cells cultured in SPro-supplemented culture media are more tolerant of oxidative stress, indicated by a dosage-dependent increase in cell viability. Investigation of the molecular mechanism of the observed increase in cell tolerance to oxidative stress revealed SPro acting as an effective antioxidant by sacrificial oxidation. Results also showed that SPro had been incorporated into cellular proteins and induced changes in protein expression profiles of treated cells. Despite being yet to determine the participation of individual factors to the observed increase of cell tolerance to oxidative stress, this study sheds light on the potential use of SPro as a dietary supplement for protecting humans from oxidative stress-associated degenerative human diseases.
氧化应激与许多人类退行性疾病的病理生理学相关，包括阿尔茨海默病、动脉粥样硬化、帕金森病和癌症。我们在之前的研究中发现，脯氨酸类似物硫代脯氨酸（SPro）在暴露于氧化剂的细胞中产生。鉴于之前观察到SPro可作为一种有效的腈捕获剂，我们在本研究中测试了以下假设：这种由氧化应激产生的半胱氨酸 - 甲醛加合物SPro可能作为一种抗氧化剂保护细胞免受氧化应激。有趣的是，结果表明，在添加了SPro的培养基中培养的HeLa细胞对氧化应激更具耐受性，细胞活力呈剂量依赖性增加表明了这一点。对观察到的细胞对氧化应激耐受性增加的分子机制的研究表明，SPro通过牺牲性氧化作为一种有效的抗氧化剂。结果还表明，SPro已被整合到细胞蛋白质中，并诱导了处理过的细胞蛋白质表达谱的变化。尽管尚未确定各个因素对观察到的细胞对氧化应激耐受性增加的参与情况，但本研究为SPro作为一种膳食补充剂用于保护人类免受氧化应激相关的退行性人类疾病的潜在用途提供了线索。
