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Hair Pigmentation (hair + pigmentation)
Selected AbstractsThe genetics of skin and hair pigmentation in manEXPERIMENTAL DERMATOLOGY, Issue 10 2006Jonathan L. Rees FMedSci No abstract is available for this article. [source] Loss-of-function variants of the human melanocortin-1 receptor gene in melanoma cells define structural determinants of receptor functionFEBS JOURNAL, Issue 24 2002Jesús Sánchez Más The ,-melanocyte-stimulating hormone (,MSH) receptor (MC1R) is a major determinant of mammalian skin and hair pigmentation. Binding of ,MSH to MC1R in human melanocytes stimulates cell proliferation and synthesis of photoprotective eumelanin pigments. Certain MC1R alleles have been associated with increased risk of melanoma. This can be theoretically considered on two grounds. First, gain-of-function mutations may stimulate proliferation, thus promoting dysplastic lesions. Second, and opposite, loss-of-function mutations may decrease eumelanin contents, and impair protection against the carcinogenic effects of UV light, thus predisposing to skin cancers. To test these possibilities, we sequenced the MC1R gene from seven human melanoma cell (HMC) lines and three giant congenital nevus cell (GCNC) cultures. Four HMC lines and two GCNC cultures contained MC1R allelic variants. These were the known loss-of-function Arg142His and Arg151Cys alleles and a new variant, Leu93Arg. Moreover, impaired response to a superpotent ,MSH analog was demonstrated for the cell line carrying the Leu93Arg allele and for a HMC line homozygous for wild-type MC1R. Functional analysis in heterologous cells stably or transiently expressing this variant demonstrated that Leu93Arg is a loss-of-function mutation abolishing agonist binding. These results, together with site-directed mutagenesis of the vicinal Glu94, demonstrate that the MC1R second transmembrane fragment is critical for agonist binding and maintenance of a resting conformation, whereas the second intracellular loop is essential for coupling to the cAMP system. Therefore, loss-of-function, but not activating MC1R mutations are common in HMC. Their study provides important clues to understand MC1R structure-function relationships. [source] Decapeptide with fibroblast growth factor (FGF)-5 partial sequence inhibits hair growth suppressing activity of FGF-5JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2003Chikako Ito Earlier studies demonstrated that knock-out of fibroblast growth factor-5 gene (Fgf-5) prolonged anagen VI phase of hair cycle, resulting long hairs in the mice. We showed the activities on hair growth of the two Fgf-5 gene products, one of which, FGF-5 suppressed hair growth by inhibiting anagen proceeding and inducing the transition from anagen to catagen, and FGF-5S, a shorter polypeptide with FGF-5-antagonizing activity translated from alternatively spliced mRNA, suppressed this activity of FGF-5. As the results suggested that FGF-5 antagonist would increase hair growth, we synthesized various peptides having partial sequences of human FGF-5 and FGF-5S and determined their FGF-5 antagonist activity. Among them, a decapeptide designated P3 (95-VGIGFHLQIY-104) that aligns with receptor binding sites of FGF-1 and FGF-2 suppressed FGF-5-induced proliferation of BALB/3T3 A31 and NIH/3T3 murine fibroblasts, and FGF receptor-1c (FGFR-1c)-transfected Ba/F3 cell line (FR-Ba/F3 cells). IC50s of this peptide on these cell proliferations were 64, 28, 146 ,M, respectively. On the other hand, IC50 of this peptide on binding of FGF-5 to the FGFR-1(IIIc)/Fc chimera was 483 ,M. Examination in dorsal depilated mice revealed that the P3 peptide reduced the activity of FGF-5 to recover hair pigmentation and hair follicle lengths. The classification of histologically observed skin sections showed FGF-5-induced delations of anagen procedure had reduced by the P3 peptide. The anti-Ki67 antibody staining of hair follicles was inhibited by administration of FGF-5, and this inhibition by FGF-5 was recovered by administration of the P3 peptide. The P3 peptide alone did not affect hair follicle length and hair cell proliferation. These results indicate that the decapeptide antagonized FGF-5 activity in vivo, and reduced the inhibition of FGF-5 in hair growth, confirming that FGF-5 inhibitors are promising substances against hair loss and/or for promoting hair growth. J. Cell. Physiol. 197: 272,283, 2003. © 2003 Wiley-Liss, Inc. [source] The discovery of the human melanocytePIGMENT CELL & MELANOMA RESEARCH, Issue 3 2006Wiete Westerhof Summary Around 2200 bc the first written description of a human pigmentation disorder, most likely vitiligo, was recorded, and from that moment the history of research into human pigmentation can be traced. For the following 4000 yr, the origins of human skin colour remained an enigma that was to generate a multitude of misconceptions. Even after European physicians began to dissect and compare dark and light coloured skin to reveal its underlying anatomy, the origins of skin and hair pigmentation were a matter of frequently erroneous speculation. The true source of human pigmentation was only finally revealed with the discovery of the melanocyte in the 19th century. Once tyrosinase was identified to be the key enzyme in pigment formation, attention focused on elucidating the chemical structure of melanin, an enterprise that remains incomplete. The developmental origins of the melanocyte were described from 1940 to 1960, and the concept of the epidermal melanin unit was introduced together with a description of the ultrastructure of the melanosome and melanosome transfer. With these advances came the realization that different skin types exhibit distinct differences at the histological level that relate to varying amounts of eumelanin and pheomelanin produced by the melanocytes. The foundation established over the past 4000 yr is the basis for all current research into this fascinating cell type. [source] Characterization of OCA2 cDNA in different porcine breeds and analysis of its potential effect on skin pigmentation in a red Iberian strainANIMAL GENETICS, Issue 2 2006A. Fernández Summary Although the function of the OCA2 gene product has not been totally clarified, variation in OCA2 has been associated with skin and hair pigmentation in human and mouse. However, its contribution to skin colour in domestic species has not been reported. In this study, cDNA and intron 9 sequences of the porcine OCA2 gene have been characterized in several pig populations. The cDNA sequence alignment of 20 animals from eight porcine populations allowed the identification of 10 single nucleotide polymorphisms (SNPs); five of the 10 SNPs were non-synonymous. The intron 9 sequence alignment of 12 animals belonging to four pig populations revealed four additional SNPs. Skin colour variation was analysed in a red strain of Iberian pigs with segregation of three SNPs forming two OCA2 intragenic haplotypes. Results from this study provide evidence of a suggestive dominant effect of haplotypes on colour intensity and indicate an important contribution of additive polygenic effects (h2 = 0.56 ± 0.21) to the variance of this trait. [source] | ||||||||||