Prodrug approach for increasing cellular glutathione levels.

Prodrug approach for increasing cellular glutathione levels.
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DOI:
10.3390/molecules15031242
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发表时间:
2010-03-03
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Di Stefano A
Di Stefano A
中科院分区:
其他
文献类型:
--
作者:
Cacciatore I;Cornacchia C;Pinnen F;Mollica A;Di Stefano A

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还原型谷胱甘肽(GSH)是哺乳动物细胞中含量最丰富的非蛋白巯基,也是多种外源性物质代谢和抗氧化防御酶的首选底物。它在许多细胞过程中起重要作用,如细胞分化、增殖和凋亡。谷胱甘肽缺乏症已在衰老和广泛的病理学中观察到,包括神经退行性疾病和囊性纤维化(CF),以及在几种病毒感染中。GSH作为治疗剂的使用是有限的,因为其不利的生物化学和药代动力学特性。一些报道提供了使用能够补充细胞内GSH水平的GSH前药的证据。这篇综述讨论了不同的策略,通过提供可逆的生物共轭物能够更容易地穿过细胞膜比GSH,并提供一个来源的巯基GSH的合成,以增加GSH的水平。
Reduced glutathione (GSH) is the most abundant non-protein thiol in mammalian cells and the preferred substrate for several enzymes in xenobiotic metabolism and antioxidant defense. It plays an important role in many cellular processes, such as cell differentiation, proliferation and apoptosis. GSH deficiency has been observed in aging and in a wide range of pathologies, including neurodegenerative disorders and cystic fibrosis (CF), as well as in several viral infections. Use of GSH as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. Several reports have provided evidence for the use of GSH prodrugs able to replenish intracellular GSH levels. This review discusses different strategies for increasing GSH levels by supplying reversible bioconjugates able to cross the cellular membrane more easily than GSH and to provide a source of thiols for GSH synthesis.
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