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Integrated structural and functional analysis of the protective effects of kinetin against oxidative stress in mammalian cellular systems
Scientific Reports
  • Muhammad Naseem, Zayed University
  • Eman M. Othman, Julius-Maximilians-Universität Würzburg
  • Moustafa Fathy, Minia University
  • Jibran Iqbal, Zayed University
  • Fares M. Howari, Zayed University
  • Fatima A. AlRemeithi, Zayed University
  • Geema Kodandaraman, Julius-Maximilians-Universität Würzburg
  • Helga Stopper, Julius-Maximilians-Universität Würzburg
  • Elena Bencurova, Julius-Maximilians-Universität Würzburg
  • Dimitrios Vlachakis, Geoponiko Panepistimion Athinon
  • Thomas Dandekar, Julius-Maximilians-Universität Würzburg
Document Type
Article
Publication Date
12-1-2020
Abstract

© 2020, The Author(s). 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.

Publisher
Nature Research
Disciplines
Keywords
  • adenine phosphoribosyltransferase,
  • adenosine receptor,
  • kinetin,
  • animal,
  • HL-60 cell line,
  • human,
  • mammal,
  • metabolism,
  • oxidation reduction reaction,
  • oxidative stress,
  • physiology,
  • tumor cell line,
  • Adenine Phosphoribosyltransferase,
  • Animals,
  • Cell Line,
  • Tumor,
  • HL-60 Cells,
  • Humans,
  • Kinetin,
  • Mammals,
  • Oxidation-Reduction,
  • Oxidative Stress,
  • Receptors,
  • Purinergic P1
Scopus ID
85089198443
Creative Commons License
Creative Commons Attribution 4.0 International
Indexed in Scopus
Yes
Open Access
Yes
Open Access Type
Gold: This publication is openly available in an open access journal/series
Citation Information
Muhammad Naseem, Eman M. Othman, Moustafa Fathy, Jibran Iqbal, et al.. "Integrated structural and functional analysis of the protective effects of kinetin against oxidative stress in mammalian cellular systems" Scientific Reports Vol. 10 Iss. 1 (2020) - 10 ISSN: <a href="https://v2.sherpa.ac.uk/id/publication/issn/2045-2322" target="_blank">2045-2322</a>
Available at: http://works.bepress.com/jibran-iqbal/75/