The coat color of mammals is primarily determined by the type, quantity, and distribution of melanin in the skin and hair. As an endogenous gas molecule, nitric oxide (NO) regulates tyrosinase production by modulating the cGMP-dependent protein kinase (PKG) pathway, which enhances melanin synthesis. However, some interrelationships have not been fully elucidated. In the present study, mouse melanocytes co-cultured with mouse keratinocytes in vitro, or as monocultures, were used as research models. The results indicated that ultraviolet B irradiation increased nitric oxide synthase (NOS) activity and NO production, and increased PKG, p21-activated kinase 4 (PAK4), and microphthalmia-associated transcription factor (MITF) levels, as well as tyrosinase (TYR), tyrosinase-related protein 1 and 2 expression, and melanin synthesis. During PKG inhibition, the expression of NO-regulated PAK4 and MITF was decreased. Pigment production was also affected, but remained higher than that in the control and NO inhibitor groups. These findings suggest that ultraviolet light regulates melanin production by activating the NO/cGMP/PKG pathway, which mediates the expression of PAK4, affecting melanin synthesis. On this basis, further elucidation of this regulatory network may improve our understanding of patterns of animal hair color formation.

哺乳动物的毛色主要由皮肤和毛发中黑色素的类型、数量和分布决定。作为一种内源性气体分子，一氧化氮 (NO) 通过调节 cGMP 依赖性蛋白激酶 (PKG) 途径来调节酪氨酸酶的产生，从而增强黑色素的合成。然而，一些相互关系尚未完全阐明。在本研究中，使用体外与小鼠角质形成细胞共培养或单一培养的小鼠黑素细胞作为研究模型。结果表明，紫外线 B 照射增加了一氧化氮合酶 (NOS) 活性和 NO 产生，并增加 PKG、p21 激活激酶 4 (PAK4) 和小眼球相关转录因子 (MITF) 以及酪氨酸酶 (TYR) 的水平、酪氨酸酶相关蛋白 1 和 2 表达以及黑色素合成。在 PKG 抑制期间，NO 调节的 PAK4 和 MITF 的表达降低。色素生成也受到影响，但仍高于对照组和 NO 抑制剂组。这些发现表明，紫外线通过激活NO/cGMP/PKG途径来调节黑色素的产生，该途径介导PAK4的表达，影响黑色素的合成。在此基础上，进一步阐明这一调控网络可能会提高我们对动物毛发颜色形成模式的理解。