PMID- 25346513
OWN - NLM
STAT- MEDLINE
DCOM- 20150727
LR  - 20141125
IS  - 1600-0625 (Electronic)
IS  - 0906-6705 (Linking)
VI  - 23
IP  - 12
DP  - 2014 Dec
TI  - DCT protects human melanocytic cells from UVR and ROS damage and increases cell 
      viability.
PG  - 916-21
LID - 10.1111/exd.12574 [doi]
AB  - Dopachrome tautomerase (DCT) is involved in the formation of the photoprotective 
      skin pigment eumelanin and has also been shown to have a role in response to 
      apoptotic stimuli and oxidative stress. The effect of DCT on UVR DNA damage 
      responses and survival pathways in human melanocytic cells was examined by 
      knockdown experiments using melanoma cells, neonatal foreskin melanoblasts (MB) 
      in monoculture and in co-culture with human keratinocytes. MB cell strains 
      genotyped as either MC1R WT or MC1R RHC homozygotes, which are known to be 
      deficient in DCT, were transduced with lentivirus vectors for either DCT 
      knockdown or overexpression. We found melanoma cell survival was reduced by DCT 
      depletion and by UVR over time. UVR-induced p53 and pp53-Ser15 levels were 
      reduced with DCT depletion. Knockdown of DCT in MC1R WT and MC1R RHC MB cells 
      reduced their survival after UVR exposure, whereas increased DCT protein levels 
      enhanced survival. DCT depletion reduced p53 and pp53-Ser15 levels in WM266-4 
      melanoma and MC1R WT MB cells, while MC1R RHC MB cells displayed variable levels. 
      Both MC1R WT and RHC genotypes of MB cells were responsive to UVR at 3 h with 
      increases in both p53 and pp53-Ser15 proteins. MC1R WT MB cell strains in 
      coculture with keratinocytes have an increased cell survival after UVR exposure 
      when compared to those in monoculture, a protective effect which appears to be 
      conferred by the keratinocytes.
CI  - (c) 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Ainger, Stephen A
AU  - Ainger SA
AD  - Institute for Molecular Bioscience, Melanogenix Group, The University of 
      Queensland, Brisbane, Qld, Australia.
FAU - Yong, Xuan L
AU  - Yong XL
FAU - Wong, Shu S
AU  - Wong SS
FAU - Skalamera, Dubravka
AU  - Skalamera D
FAU - Gabrielli, Brian
AU  - Gabrielli B
FAU - Leonard, J Helen
AU  - Leonard JH
FAU - Sturm, Richard A
AU  - Sturm RA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - Exp Dermatol
JT  - Experimental dermatology
JID - 9301549
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptor, Melanocortin, Type 1)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.3.12 (dopachrome isomerase)
SB  - IM
MH  - Cell Survival/*radiation effects
MH  - Coculture Techniques
MH  - DNA Damage
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Intramolecular Oxidoreductases/antagonists & inhibitors/genetics/*metabolism
MH  - Keratinocytes/metabolism
MH  - Melanocytes/cytology/*metabolism/*radiation effects
MH  - Melanoma/genetics/metabolism/pathology
MH  - RNA, Small Interfering/genetics
MH  - Reactive Oxygen Species/metabolism
MH  - Receptor, Melanocortin, Type 1/genetics/metabolism
MH  - Ultraviolet Rays/*adverse effects
MH  - Up-Regulation
OTO - NOTNLM
OT  - Dopachrome tautomerase
OT  - melanocortin-1 receptor
OT  - melanocyte
OT  - melanoma
OT  - p53
OT  - pigmentation
EDAT- 2014/10/28 06:00
MHDA- 2015/07/28 06:00
CRDT- 2014/10/28 06:00
PHST- 2014/10/20 00:00 [accepted]
PHST- 2014/10/28 06:00 [entrez]
PHST- 2014/10/28 06:00 [pubmed]
PHST- 2015/07/28 06:00 [medline]
AID - 10.1111/exd.12574 [doi]
PST - ppublish
SO  - Exp Dermatol. 2014 Dec;23(12):916-21. doi: 10.1111/exd.12574.