DCT protects human melanocytic cells from UVR and ROS damage and increases cell viability

Ainger, Stephen A., Yong, Xuan L., Wong, Shu S., Skalamera, Dubravka, Gabrielli, Brian, Leonard, J. Helen and Sturm, Richard A. (2014) DCT protects human melanocytic cells from UVR and ROS damage and increases cell viability. Experimental Dermatology, 23 12: 916-921. doi:10.1111/exd.12574

Author Ainger, Stephen A.
Yong, Xuan L.
Wong, Shu S.
Skalamera, Dubravka
Gabrielli, Brian
Leonard, J. Helen
Sturm, Richard A.
Title DCT protects human melanocytic cells from UVR and ROS damage and increases cell viability
Journal name Experimental Dermatology   Check publisher's open access policy
ISSN 1600-0625
Publication date 2014-12-01
Sub-type Article (original research)
DOI 10.1111/exd.12574
Open Access Status
Volume 23
Issue 12
Start page 916
End page 921
Total pages 6
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2015
Language eng
Abstract 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.
Keyword Dopachrome tautomerase
Melanocortin-1 receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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Created: Tue, 06 Jan 2015, 09:02:27 EST by Susan Allen on behalf of Institute for Molecular Bioscience