TY  - JOUR
A1  - Othman, Eman M.
A1  - Naseem, Muhammed
A1  - Awad, Eman
A1  - Dandekar, Thomas
A1  - Stopper, Helga
T1  - The Plant Hormone Cytokinin Confers Protection against Oxidative Stress in Mammalian Cells
JF  - PLoS One
N2  - Modulating key dynamics of plant growth and development, the effects of the plant hormone cytokinin on animal cells gained much attention recently. Most previous studies on cytokinin effects on mammalian cells have been conducted with elevated cytokinin concentration (in the μM range). However, to examine physiologically relevant dose effects of cytokinins on animal cells, we systematically analyzed the impact of kinetin in cultured cells at low and high concentrations (1nM-10μM) and examined cytotoxic and genotoxic conditions. We furthermore measured the intrinsic antioxidant activity of kinetin in a cell-free system using the Ferric Reducing Antioxidant Power assay and in cells using the dihydroethidium staining method. Monitoring viability, we looked at kinetin effects in mammalian cells such as HL60 cells, HaCaT human keratinocyte cells, NRK rat epithelial kidney cells and human peripheral lymphocytes. Kinetin manifests no antioxidant activity in the cell free system and high doses of kinetin (500 nM and higher) reduce cell viability and mediate DNA damage in vitro. In contrast, low doses (concentrations up to 100 nM) of kinetin confer protection in cells against oxidative stress. Moreover, our results show that pretreatment of the cells with kinetin significantly reduces 4-nitroquinoline 1-oxide mediated reactive oxygen species production. Also, pretreatment with kinetin retains cellular GSH levels when they are also treated with the GSH-depleting agent patulin. Our results explicitly show that low kinetin doses reduce apoptosis and protect cells from oxidative stress mediated cell death. Future studies on the interaction between cytokinins and human cellular pathway targets will be intriguing.
KW  - DNA damage
KW  - apoptosis
KW  - oxidative stress
KW  - fluorescence recovery after photobleaching
KW  - lymphocytes
KW  - antioxidants
KW  - cell staining
KW  - cytokinins
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147983
VL  - 11
IS  - 12
ER  - 
TY  - JOUR
A1  - Naseem, Muhammad
A1  - Othman, Eman M.
A1  - Fathy, Moustafa
A1  - Iqbal, Jibran
A1  - Howari, Fares M.
A1  - AlRemeithi, Fatima A.
A1  - Kodandaraman, Geema
A1  - Stopper, Helga
A1  - Bencurova, Elena
A1  - Vlachakis, Dimitrios
A1  - Dandekar, Thomas
T1  - Integrated structural and functional analysis of the protective effects of kinetin against oxidative stress in mammalian cellular systems
JF  - Scientific Reports
N2  - 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.
KW  - cytokinins
KW  - 6-benzylaminopurine
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231317
VL  - 10
ER  -