PMID- 23710286
OWN - NLM
STAT- MEDLINE
DCOM- 20140813
LR  - 20211021
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2013
DP  - 2013
TI  - Curcumin protects human keratinocytes against inorganic arsenite-induced acute 
      cytotoxicity through an NRF2-dependent mechanism.
PG  - 412576
LID - 10.1155/2013/412576 [doi]
LID - 412576
AB  - 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 muM) also increased protein expression of long isoforms of NRF1. 
      Treatment with low concentrations of curcumin (2.5 or 5 muM) 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.
FAU - Zhao, Rui
AU  - Zhao R
AD  - Department of Forensic Pathology, School of Forensic Medicine, China Medical 
      University, Shenyang, Liaoning 110001, China.
FAU - Yang, Bei
AU  - Yang B
FAU - Wang, Linlin
AU  - Wang L
FAU - Xue, Peng
AU  - Xue P
FAU - Deng, Baocheng
AU  - Deng B
FAU - Zhang, Guohua
AU  - Zhang G
FAU - Jiang, Shukun
AU  - Jiang S
FAU - Zhang, Miao
AU  - Zhang M
FAU - Liu, Min
AU  - Liu M
FAU - Pi, Jingbo
AU  - Pi J
FAU - Guan, Dawei
AU  - Guan D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130421
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Antioxidants)
RN  - 0 (Arsenites)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Protective Agents)
RN  - 0 (RNA, Messenger)
RN  - EC 1.13.12.- (Luciferases)
RN  - IT942ZTH98 (Curcumin)
RN  - N5509X556J (arsenite)
SB  - IM
MH  - Antioxidants/metabolism
MH  - Apoptosis/drug effects
MH  - Arsenites/*toxicity
MH  - Curcumin/*pharmacology
MH  - Cytoprotection/*drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Keratinocytes/drug effects/*metabolism/*pathology
MH  - Luciferases/metabolism
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Protective Agents/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Response Elements/genetics
PMC - PMC3654359
EDAT- 2013/05/28 06:00
MHDA- 2014/08/15 06:00
PMCR- 2013/04/21
CRDT- 2013/05/28 06:00
PHST- 2013/02/05 00:00 [received]
PHST- 2013/03/18 00:00 [accepted]
PHST- 2013/05/28 06:00 [entrez]
PHST- 2013/05/28 06:00 [pubmed]
PHST- 2014/08/15 06:00 [medline]
PHST- 2013/04/21 00:00 [pmc-release]
AID - 10.1155/2013/412576 [doi]
PST - ppublish
SO  - Oxid Med Cell Longev. 2013;2013:412576. doi: 10.1155/2013/412576. Epub 2013 Apr 
      21.