title: The Plant Hormone Cytokinin Confers Protection against Oxidative Stress in Mammalian Cells.
abstract: 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.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.|Department of Analytical Chemistry, Faculty of Pharmacy, University of El-Minia, Minia, Egypt.
authors.forename: Eman M
authors.initials: EM
authors.lastname: Othman
authors.affiliation: Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany.|Bogazici University, Department of Molecular Biology and Genetics, Kuzey Park, Istanbul.
authors.forename: Muhammed
authors.initials: M
authors.lastname: Naseem
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.
authors.forename: Eman
authors.initials: E
authors.lastname: Awad
authors.affiliation: Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0003-1886-7625
authors.initials: T
authors.lastname: Dandekar
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Stopper
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003583:Cytokinins / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010937:Plant Growth Regulators / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003583:Cytokinins; D010937:Plant Growth Regulators; D017382:Reactive Oxygen Species