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Liver X receptor activation inhibits melanogenesis through the acceleration of ERK-mediated MITF degradation

Title
Liver X receptor activation inhibits melanogenesis through the acceleration of ERK-mediated MITF degradation
Authors
Lee C.S.Park M.Han J.Lee J.-H.Bae I.-H.Choi H.Son E.D.Park Y.-H.Lim K.-M.
Ewha Authors
임경민
SCOPUS Author ID
임경민scopus
Issue Date
2013
Journal Title
Journal of Investigative Dermatology
ISSN
0022-202XJCR Link
Citation
vol. 133, no. 4, pp. 1063 - 1071
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Liver X receptors (LXRs) are nuclear receptors that act as ligand-activated transcription factors regulating lipid metabolism and inflammation. In the skin, activation of LXRs stimulates differentiation of keratinocytes and augments lipid synthesis in sebocytes. However, the function of LXRs in melanocytes remains largely unknown. We investigated whether LXR activation would affect melanogenesis. In human primary melanocytes, MNT-1, and B16 melanoma cells, TO901317, a synthetic LXR ligand, inhibited melanogenesis. Small interfering RNA (siRNA) experiments revealed the dominant role of LXRβ in TO901317-mediated antimelanogenesis. Enzymatic activities of tyrosinase were unaffected, but the expression of tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2 was suppressed by TO901317. Expressions of microphthalmia-associated transcription factor (MITF), a master transcriptional regulator of melanogenesis, and cAMP-responsive element-binding activation were not affected. It is noteworthy that the degradation of MITF was accelerated by TO901317. Extracellular signal-regulated kinase (ERK) contributed to TO901317-induced antimelanogenesis, which was evidenced by recovery of melanogenesis with ERK inhibitor. Other LXR ligands, 22(R)-hydroxycholesterol (22(R)HC) and GW3965, also activated ERK and suppressed melanogenesis. The intermediary role of Ras was confirmed in TO901317-induced ERK phosphorylation. Finally, antimelanogenic effects of TO901317 were confirmed in vivo in UVB-tanning model in brown guinea pigs, providing a previously unreported line of evidence that LXRs may be important targets for antimelanogenesis. © 2013 The Society for Investigative Dermatology.
DOI
10.1038/jid.2012.409
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약학대학 > 약학과 > Journal papers
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