Resveratrol induces human keratinocyte damage via the activation of class III histone deacetylase, Sirt1.
Human skin diseases are various and induce chronic inflammatory disorders, including psoriasis, atopic dermatitis and certain forms of ichthyosis. Psoriasis is a chronic inflammatory skin disease characterized by circumscribed, red, thickened plaques. Regulation of the balance between growth, differentiation and death is critical to keratinocytes; when altered, epidermal keratinocytes undergo hyperproliferation, abnormal differentiation and inflammatory infiltration. In the present study, we focused on the effects of resveratrol, found in red wine and peanuts, on the cell death of keratinocytes. We additionally studied the mechanism of resveratrol on Sirt1, a class III histone deacetylase, and Akt phosphorylation. Resveratrol caused apoptosis and increased Sirt1 expression in human HaCaT keratinocytes, following a decrease in the p62 protein level. Inhibition of Sirt1 by Sirt1 inhibitor restored cell viability and protein levels. Furthermore, we showed that resveratrol-induced Sirt1 blocked Akt phosphorylation. The present results indicated that resveratrol inhibited the Akt pathways by inducing Sirt1, thus leading to cell death. These data suggest that resveratrol-mediated activation of Sirt1 histone deacetylase may be a potential therapeutic target for skin diseases including psoriasis.
Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea.
Ju-Hee
JH
Lee
Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea.
Jin-Shang
JS
Kim
Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea.
Sang-Youel
SY
Park
Biosafety Research Institute, Department of Biochemistry, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea.
You-Jin
YJ
Lee
D017209:Apoptosis; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000633:toxicity*
C118585:P62 protein, human; D016601:RNA-Binding Proteins; D013267:Stilbenes; D051057:Proto-Oncogene Proteins c-akt; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol