Integrated structural and functional analysis of the protective effects of kinetin against oxidative stress in mammalian cellular systems.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 08 2020
07 08 2020
Historique:
received:
28
01
2020
accepted:
16
07
2020
entrez:
10
8
2020
pubmed:
10
8
2020
medline:
17
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32770053
doi: 10.1038/s41598-020-70253-1
pii: 10.1038/s41598-020-70253-1
pmc: PMC7414151
doi:
Substances chimiques
Receptors, Purinergic P1
0
Adenine Phosphoribosyltransferase
EC 2.4.2.7
Kinetin
P39Y9652YJ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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