Curcumin Protects Human Keratinocytes against Inorganic Arsenite-Induced Acute Cytotoxicity through an NRF2-Dependent Mechanism. (21st April 2013)

• Record Type: Journal Article
• Authors: Zhao, Rui; Yang, Bei; Wang, Linlin; Xue, Peng; Deng, Baocheng; Zhang, Guohua; Jiang, Shukun; Zhang, Miao; Liu, Min; Pi, Jingbo; Guan, Dawei
• Other Names: Cho Hye-Youn Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2013(2013)
• Publication Date: 2013-04-21
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2013/412576
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Human exposure to inorganic arsenic leads to various dermal disorders, including hyperkeratosis and skin cancer. Curcumin is demonstrated to induce remarkable antioxidant activity in a variety of cells and tissues. The present study aimed at identifying curcumin as a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2) and demonstrating its protective effect against inorganic arsenite- (iAs 3+ -) induced cytotoxicity in human keratinocytes. We found that curcumin led to nuclear accumulation of NRF2 protein and increased the expression of antioxidant response element- (ARE-) regulated genes in HaCaT keratinocytes in concentration- and time-dependent manners. High concentration of curcumin (20 μ M) also increased protein expression of long isoforms of NRF1. Treatment with low concentrations of curcumin (2.5 or 5 μ M) effectively increased the viability and survival of HaCaT cells against iAs 3+ -induced cytotoxicity as assessed by the MTT assay and flow cytometry and also attenuated iAs 3+ -induced expression of cleaved caspase-3 and cleaved PARP protein. Selective knockdown of NRF2 or KEAP1 by lentiviral shRNAs significantly diminished the cytoprotection conferred by curcumin, suggesting that the protection against iAs 3+ -induced cytotoxicity is dependent on the activation of NRF2. Our results provided a proof of the concept of using curcumin to activate the NRF2 pathway to alleviate arsenic-induced dermal damage.