Department of Life and Environmental Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi, UAE.
Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, Wuerzburg, Germany.
Sci Rep. 2020 Aug 7;10(1):13330. doi: 10.1038/s41598-020-70253-1.
Metabolism and signaling of cytokinins was first established in plants, followed by cytokinin discoveries in all kingdoms of life. However, understanding of their role in mammalian cells is still scarce. Kinetin is a cytokinin that mitigates the effects of oxidative stress in mammalian cells. The effective concentrations of exogenously applied kinetin in invoking various cellular responses are not well standardized. Likewise, the metabolism of kinetin and its cellular targets within the mammalian cells are still not well studied. Applying vitality tests as well as comet assays under normal and hyper-oxidative states, our analysis suggests that kinetin concentrations of 500 nM and above cause cytotoxicity as well as genotoxicity in various cell types. However, concentrations below 100 nM do not cause any toxicity, rather in this range kinetin counteracts oxidative burst and cytotoxicity. We focus here on these effects. To get insights into the cellular targets of kinetin mediating these pro-survival functions and protective effects we applied structural and computational approaches on two previously testified targets for these effects. Our analysis deciphers vital residues in adenine phosphoribosyltransferase (APRT) and adenosine receptor (A2A-R) that facilitate the binding of kinetin to these two important human cellular proteins. We finally discuss how the therapeutic potential of kinetin against oxidative stress helps in various pathophysiological conditions.
细胞分裂素的代谢和信号转导首先在植物中建立，随后在所有生命领域都发现了细胞分裂素。然而，人们对其在哺乳动物细胞中的作用仍知之甚少。激动素是一种细胞分裂素，可减轻哺乳动物细胞中氧化应激的影响。外源性激动素在引发各种细胞反应中的有效浓度尚未得到很好的标准化。同样，激动素在哺乳动物细胞内的代谢及其细胞靶标也尚未得到很好的研究。通过在正常和超氧化状态下进行活力测试和彗星试验，我们的分析表明，500 nM 及以上浓度的激动素会导致各种细胞类型的细胞毒性和遗传毒性。然而，浓度低于 100 nM 不会引起任何毒性，相反，在这个范围内，激动素可以对抗氧化爆发和细胞毒性。我们在这里重点关注这些效应。为了深入了解激动素介导这些生存促进功能和保护作用的细胞靶标，我们在两个先前证明对这些效应有作用的靶标上应用了结构和计算方法。我们的分析揭示了在腺嘌呤磷酸核糖基转移酶（APRT）和腺苷受体（A2A-R）中促进激动素与这两种重要的人类细胞蛋白结合的关键残基。最后，我们讨论了激动素对氧化应激的治疗潜力如何帮助各种病理生理状况。
