Bertolesi Gabriel E, Debnath Nilakshi, Heshami Neda, Bui Ryan, Zadeh-Haghighi Hadi, Simon Christoph, McFarlane Sarah
Department of Cell Biology and Anatomy, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Pigment Cell Melanoma Res. 2025 Jan;38(1):e13220. doi: 10.1111/pcmr.13220.
Circadian regulation of skin pigmentation is essential for thermoregulation, ultraviolet (UV) protection, and synchronization of skin cell renewal. This regulation involves both cell-autonomous photic responses and non-cell-autonomous hormonal control, particularly through melatonin produced in a light-sensitive manner. Photosensitive opsins, cryptochromes, and melatonin regulate circadian rhythms in skin pigment cells. We studied light/dark cycles and melatonin coordination in melanin synthesis and cell proliferation of Xenopus laevis melanophores. In vivo, tadpole pigmentation shows robust circadian regulation mainly hormone-driven, in that isolated melanophores respond strongly to melatonin but only slightly to light. Melanophore proliferation is faster in the dark and slower with melatonin as compared to a 12/12 light/dark cycle. Expression of circadian core genes (clock, bmal1, per1, per2, per3, cry1, cry2, and cry4) in melatonin-treated cells during the light phase mimics dark phase expression. Overexpression of individual Crys did not affect melanization or cell proliferation, likely due to their cooperative actions. Melanin synthesis was inhibited by circadian cycle deregulation through (a) pharmacological inhibition of Cry1 and Cry2 degradation with KL001, (b) continuous light or dark conditions, and (c) melatonin treatment. Our findings suggest that circadian cycle regulation, rather than proliferative capacity, alters melanization of melanophores.
皮肤色素沉着的昼夜节律调节对于体温调节、紫外线防护以及皮肤细胞更新的同步化至关重要。这种调节涉及细胞自主的光反应和非细胞自主的激素控制，特别是通过以光敏感方式产生的褪黑素。光敏视蛋白、隐花色素和褪黑素调节皮肤色素细胞中的昼夜节律。我们研究了非洲爪蟾黑素细胞中光/暗周期和褪黑素在黑色素合成及细胞增殖中的协调作用。在体内，蝌蚪色素沉着显示出主要由激素驱动的强大昼夜节律调节，即分离的黑素细胞对褪黑素反应强烈，但对光反应微弱。与12/12光/暗周期相比，黑素细胞在黑暗中增殖更快，而在有褪黑素时增殖更慢。在光照阶段，经褪黑素处理的细胞中昼夜节律核心基因（clock、bmal1、per1、per2、per3、cry1、cry2和cry4）的表达模拟黑暗阶段的表达。单个隐花色素的过表达不影响黑色素生成或细胞增殖，可能是由于它们的协同作用。通过以下方式扰乱昼夜节律周期可抑制黑色素合成：（a）用KL001药理学抑制Cry1和Cry2降解，（b）持续光照或黑暗条件，以及（c）褪黑素处理。我们的研究结果表明，昼夜节律周期调节而非增殖能力改变了黑素细胞的黑色素生成。
