Inhibition of UVB-induced oxidative stress-mediated phosphorylation of mitogen-activated protein kinase signaling pathways in cultured human epidermal keratinocytes by green tea polyphenol (-)-epigallocatechin-3-gallate.
Exposure of normal human epidermal keratinocytes (NHEK) to UVB radiation induces intracellular release of hydrogen peroxide (oxidative stress) and phosphorylation of mitogen-activated protein kinase cell signaling pathways. Here, we demonstrate that pretreatment of NHEK with (-)-epigallocatechin-3-gallate (EGCG), an antioxidant from green tea, inhibits UVB-induced hydrogen peroxide (H(2)O(2)) production and H(2)O(2)-mediated phosphorylation of MAPK signaling pathways. We found that treatment of EGCG (20 microg/ml of media) to NHEK before UVB (30 mJ/cm(2)) exposure inhibited UVB-induced H(2)O(2) production (66-80%) concomitant with the inhibition of UVB-induced phosphorylation of ERK1/2 (57-80%), JNK (53-83%), and p38 (50-77%) proteins. To demonstrate whether UVB-induced phosphorylation of MAPK occurs via UVB-induced H(2)O(2) (oxidative stress) production, NHEK were treated with the oxidant H(2)O(2). Treatment of H(2)O(2) to NHEK resulted in phosphorylation of ERK1/2, JNK, and p38. Using the same in vitro system, when these cells were pretreated with EGCG or with the known antioxidant ascorbic acid (as positive control), H(2)O(2)-induced phosphorylation of ERK1/2, JNK, and p38 was found to be significantly inhibited. These findings demonstrate that EGCG has the potential to inhibit UVB-induced oxidative stress-mediated phosphorylation of MAPK signaling pathways, suggesting that EGCG could be useful in attenuation of oxidative stress-mediated and MAPK-caused skin disorders in humans.
Katiyar
S K
SK
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA. shatiyar@uab.edu
Afaq
F
F
Azizuddin
K
K
Mukhtar
H
H
D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System / Q000502:physiology* / Q000528:radiation effects*; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology* / Q000528:radiation effects*; D010766:Phosphorylation; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
D000975:Antioxidants; D016877:Oxidants; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D001205:Ascorbic Acid