Free Communications : P6 ; (2RS,4R)-2-(2,3-Dihydroxyphenyl)Thiazolidine-4-Carboxylic acid (MHY384) Inhibits NO-induced Melanogenesis Via Regulation of cGMP Signaling Pathway = Free Communications : P6 ; (2RS,4R)-2-(2,3-Dihydroxyphenyl)Thiazolidine-4-Carboxylic acid (MHY384) Inhibits NO-induced Melanogenesis Via Regulation of cGMP Signaling Pathway

다국어 초록 (Multilingual Abstract)

During the process of melanogenesis, oxidative stress which is one of the main causes of melanocyte damage, is generated from various sources including reactive intermediates, such as NO, and melanin intermediates with oxidant properties. It has been found that NO and NO-induced cyclic guanosine monophosphate (cGMP) pathway plays an important role in Ultraviolet B (UVB)-induced melanogenesis via induction of tyrosinase expression. In an attempt to find a novel compound reducing oxidative stress and melanogenesis, we evaluated anti-inflammatory and NO scavenging effects of (2RS,4R)-2-(2,3- dihydroxyphenyl)thiazolidine-4-carboxylic acid (MHY384) in vitro and in vivo. The purpose of this study is to investigate the effect of MHY384 on NO mediated melanogenesis in vitro and in vivo, using B16F10 melanoma cell and melanin-possessing hairless mice, HRM2 models, respectively. The NO scavenging activity of MHY384 was evaluated in cell-free system. Our in vitro study determined that MHY384 inhibited melanogenesis via regulating tyrosinase activity by NO-induced cGMP signaling pathway in B16F10 melanoma cells. In vivo experiment was conducted in HRM2 hairless mouse mice which are pre-treated with MHY384 and then irradiated with UVB repeatedly. Expressions of phosphorylated cAMP response element-binding protein (pCREB), tyrosinase, and nuclear Microphthalmia-associated transcription factor (MITF), and NO, peroxynitrite and reactive oxygen species (ROS) were measured by morphological, histological or biochemical analyses.MHY-384 was proved to be effective at scavenging nitric oxide (NO), which serves as an important modulator in the melanogenesis signaling pathway. MHY-384 significantly inhibited 200 μM sodium nitroprusside (SNP, a NO donor)-induced NO generation in dose dependent manner. In addition, MHY-384 suppressed tyrosinase activity and melanin synthesis induced by SNP in B16F10 melanoma cells. The effect of MHY-384 on NO-mediated pathway was also investigated. The gene expressions of tyrosinase and MITF and the protein level of pCREB, which are normally increased by UVB and oxidative stress, were down-regulated by MHY-384. HRM2 hairless mice were used to evaluate anti-melanogenic effects of MHY384 in vivo. It was found that MHY-384 modulated UVB-induced morphological, histological and biochemical changes, such as expression of tyrosinase and nuclear MITF and production of NO, ONOO? and ROS. In conclusion, MHY-384 inhibited NO-mediated melanogenesis by direct NO scavenging as well as reducing the expression of tyrosinase via NO/cGMP signaling pathway. It might be utilized for the development of a new candidate for treatment of the hyper-pigmentation disorders.