Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light
Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light
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DOI：
10.1152/ajpcell.00092.2009
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发表时间：
2009-09-01
影响因子：
5.5
通讯作者：
Setaluri, Vijayasaradhi
中科院分区：
文献类型：
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作者：
Devi, Sulochana;Kedlaya, Rajendra;Setaluri, Vijayasaradhi
Devi S，Kedlaya R，Maddodi N，Bhat KM，Weber CS，Valdivia H，Setaluri V.人类黑素细胞中的钙稳态：瞬时受体电位melastatin 1（TRPM 1）的作用及其通过紫外线的调节。美国生理学杂志细胞生理学297：C679-C687，2009年。首次发表于2009年7月8日; doi：10.1152/ajpcell.00092.2009。瞬时受体电位melastatin（TRPM）是一个亚家族的离子通道，参与感知味道，环境温度，低pH值，渗透压和化学配体。Melastatin 1/TRPM 1是黑色素瘤的创始成员，最初被鉴定为黑色素瘤转移抑制因子，这是基于其在皮肤和眼睛中的正常色素细胞中的表达，而不是在侵袭性、转移能力黑色素瘤中的表达。TRPM 1及其在正常黑素细胞和黑色素瘤进展中的调节作用尚不清楚。在这里，我们研究了TRPM 1的表达与人表皮黑素细胞的生长和分化的关系。TRPM 1表达和细胞内Ca 2+水平在快速增殖的黑素细胞中显著低于缓慢生长的分化黑素细胞。我们发现，慢病毒短发夹RNA（shRNA）介导的TRPM 1敲低导致细胞内Ca 2+减少和Ca 2+摄取减少，表明TRPM 1在黑素细胞中的Ca 2+稳态中的作用。TRPM 1敲低也导致酪氨酸酶活性和细胞内黑色素减少。通过转染或通过紫外线B辐射诱导内源性p53表达肿瘤抑制因子p53，导致TRPM 1表达的抑制，伴随着细胞内Ca 2+动员和细胞外Ca 2+摄取的减少。这些数据表明TRPM 1介导的Ca 2+稳态，这也是由紫外线B，在黑素生成的作用。
Devi S, Kedlaya R, Maddodi N, Bhat KM, Weber CS, Valdivia H, Setaluri V. Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light. Am J Physiol Cell Physiol 297: C679-C687, 2009. First published July 8, 2009; doi:10.1152/ajpcell.00092.2009.-Transient receptor potential melastatin (TRPM) is a subfamily of ion channels that are involved in sensing taste, ambient temperature, low pH, osmolarity, and chemical ligands. Melastatin 1/TRPM1, the founding member, was originally identified as melanoma metastasis suppressor based on its expression in normal pigment cells in the skin and the eye but not in aggressive, metastasis-competent melanomas. The role of TRPM1 and its regulation in normal melanocytes and in melanoma progression is not understood. Here, we studied the relationship of TRPM1 expression to growth and differentiation of human epidermal melanocytes. TRPM1 expression and intracellular Ca2+ levels are significantly lower in rapidly proliferating melanocytes compared to the slow growing, differentiated melanocytes. We show that lentiviral short hairpin RNA (shRNA)-mediated knockdown of TRPM1 results in reduced intracellular Ca2+ and decreased Ca2+ uptake suggesting a role for TRPM1 in Ca2+ homeostasis in melanocytes. TRPM1 knockdown also resulted in a decrease in tyrosinase activity and intracellular melanin pigment. Expression of the tumor suppressor p53 by transfection or induction of endogenous p53 by ultraviolet B radiation caused repression of TRPM1 expression accompanied by decrease in mobilization of intracellular Ca2+ and uptake of extracellular Ca2+. These data suggest a role for TRPM1-mediated Ca2+ homeostasis, which is also regulated by ultraviolet B, in melanogenesis.