Hydroxytyrosol inhibits hydrogen peroxide-induced apoptotic signaling via labile iron chelation.
Although it is known that Mediterranean diet plays an important role in maintaining human health, the underlying molecular mechanisms remain largely unknown. The aim of this investigation was to elucidate the potential role of ortho-dihydroxy group containing natural compounds in H2O2-induced DNA damage and apoptosis. For this purpose, the main phenolic alcohols of olive oil, namely hydroxytyrosol and tyrosol, were examined for their ability to protect cultured cells under conditions of oxidative stress. A strong correlation was observed between the ability of hydroxytyrosol to mitigate intracellular labile iron level and the protection offered against H2O2-induced DNA damage and apoptosis. On the other hand, tyrosol, which lacks the ortho-dihydroxy group, was ineffective. Moreover, hydroxytyrosol (but not tyrosol), was able to diminish the late sustained phase of H2O2-induced JNK and p38 phosphorylation. The derangement of intracellular iron homeostasis, following exposure of cells to H2O2, played pivotal role both in the induction of DNA damage and the initiation of apoptotic signaling. The presented results suggest that the protective effects exerted by ortho-dihydroxy group containing dietary compounds against oxidative stress-induced cell damage are linked to their ability to influence changes in the intracellular labile iron homeostasis.
Laboratory of Biological Chemistry, University of Ioannina, School of Health Sciences, Faculty of Medicine, 451 10 Ioannina, Greece.
Natalia
N
Kitsati
Laboratory of Biological Chemistry, University of Ioannina, School of Health Sciences, Faculty of Medicine, 451 10 Ioannina, Greece.
Michalis D
MD
Mantzaris
Laboratory of Biological Chemistry, University of Ioannina, School of Health Sciences, Faculty of Medicine, 451 10 Ioannina, Greece. Electronic address: dgalaris@uoi.gr.
Dimitrios
D
Galaris
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D019169:Jurkat Cells; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D000069463:Olive Oil / Q000737:chemistry; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000975:Antioxidants; D000069463:Olive Oil; C005975:3,4-dihydroxyphenylethanol; C011867:4-hydroxyphenylethanol; D006861:Hydrogen Peroxide; D007501:Iron; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D010626:Phenylethyl Alcohol
Apoptosis; Hydroxytyrosol; Labile iron; Mitogen activated protein kinases; Redox signaling; Tyrosol