硒谷胱甘肽二硒化物的抗氧化和抗糖化应激活性

Pharmaceuticals Pub Date : 2024-08-09 DOI:10.3390/ph17081049
Akiko Kanamori, Nana Egawa, Suyako Yamasaki, Takehito Ikeda, M. J. da Rocha, C. F. Bortolatto, L. Savegnago, C. A. Brüning, Michio Iwaoka
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摘要

氧化和糖化压力对细胞造成的损害每天都在累积,并加速衰老。谷胱甘肽(GSH)是生物体内一种主要的抗氧化分子,在解毒细胞中固有的导致压力的物质(如 H2O2 和甲基乙二醛(MG),后者是高级糖化终产物(AGEs)的一种重要中间体)方面发挥着至关重要的作用。 在这项研究中,我们重点研究了 GSH 的硒类似物(即硒谷胱甘肽(GSeH))与 GSH 相比所增强的抗氧化能力,并考察了其对人体的影响、与 GSH 相比,硒谷胱甘肽(GSeH)的抗氧化能力更强,我们还考察了它在解毒应激物质和提高细胞活力方面的作用。在无细胞系统中,由 GSeSeG 在 NADPH 和谷胱甘肽还原酶(GR)存在下原位生成的 GSeH(1 mM)可迅速还原 80% 以上的 0.1 mM H2O2,这表明 GSeSeG 具有类似谷胱甘肽过氧化物酶(GPx)的显著抗氧化活性。同样,0.5 mM GSeH 在 30 分钟内通过非酶促机制降解了约 50% 的 0.5 mM MG。研究还发现,GSeSeG(0.05-0.5 mM)对 1-氯-2,4-二硝基苯(CDNB)具有类似谷胱甘肽 S 转移酶(GST)的活性。同时,经 GSeSeG 预处理的 HeLa 细胞对 1.2 mM H2O2([GSeSeG] = 0.5-50 μM)和 4 mM MG([GSeSeG] = 3 μM)表现出更高的存活率,且后者的效果可维持两天。因此,GSeSeG 是一种潜在的细胞抗氧化剂和抗糖化应激剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antioxidative and Antiglycative Stress Activities of Selenoglutathione Diselenide
The damage caused by oxidative and glycative stress to cells accumulates on a daily basis and accelerates aging. Glutathione (GSH), a major antioxidant molecule in living organisms, plays a crucial role in detoxifying the stress-causing substances inherent in cells, such as H2O2 and methylglyoxal (MG), an important intermediate of advanced glycation end-products (AGEs). In this study, we focused on the enhanced antioxidant capacity of the selenium analog of GSH, i.e., selenoglutathione (GSeH), compared to GSH, and examined its effects on the detoxification of stress-causing substances and improvement in cell viability. In cell-free systems, GSeH (1 mM) generated in situ from GSeSeG in the presence of NADPH and glutathione reductase (GR) rapidly reduced more than 80% of 0.1 mM H2O2, indicating the significant glutathione peroxidase (GPx)-like antioxidant activity of GSeSeG. Similarly, around 50% of 0.5 mM MG was degraded by 0.5 mM GSeH within 30 min through a non-enzymatic mechanism. It was also found that GSeSeG (0.05–0.5 mM) showed glutathione S-transferase (GST)-like activity against 1-chloro-2,4-dinitrobenzene (CDNB), a model substance of oxidative stress-causing toxic materials in cells. Meanwhile, HeLa cells that had been pre-treated with GSeSeG exhibited increased viability against 1.2 mM H2O2 (at [GSeSeG] = 0.5–50 μM) and 4 mM MG (at [GSeSeG] = 3 μM), and the latter effect was maintained for two days. Thus, GSeSeG is a potential antioxidant and antiglycative stress agent for cells.
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