NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis
文献类型：期刊论文
| 作者 | Shang, Jing3,4,5,7; He, Ling6; Jin, Yu1; Liu, Meng2; Xia, Zhenjiang3; An, Xiaohong4,5,7; Fu, Mengsi4,5,7; Pan, Qi4,5,7; Cai, Minxuan4,5,7; Huang, Qiaoling4,5,7 |
| 刊名 | FASEB JOURNAL
 |
| 出版日期 | 2018-06-01 |
| 卷号 | 32期号:6页码:3193-3214 |
| 关键词 | Protein-protein Interaction Signaling Cascades Nk1r 5-ht1ar Heterdimerization |
| ISSN号 | 0892-6638 |
| DOI | 10.1096/fj.201700564RR |
| 文献子类 | Article |
| 英文摘要 | Substance P (SP) is a candidate mediator along the brain-skin axis and can mimic the effects of stress to regulate melanogenesis. Previously, we and others have found that the regulation of SP for pigmentary function was mediated by neurokinin 1 receptor (NK1R). Emerging evidence has accumulated that psychologic stress can induce dysfunction in the cutaneous serotonin 5-hydroxytryptamine (5-HT)-5-HT1A/1B receptor system, thereby resulting in skin hypopigmentation. Moreover, NK1R and 5-HTR (except 5-HT3) belong to GPCR. The present study aimed at assessing the possible existence of NK1R-5-HTR interactions and related melanogenic functions. Western blot and PCR detection revealed that SP reduced expression of 5-HT1A receptor via the NK1 receptor. Biochemical analyses showed that NK1R and 5-HT1AR could colocalize and interact in a cell and in the skin. When the N terminus of the NK1R protein was removed NK1R surface targeting was prevented, the interaction between NK1R-5-HT1AR decreased, and the depigmentation caused by SP and WAY100635 could be rescued. Importantly, pharmaceutical coadministration of NK1R agonist (SP) and 5-HT1A antagonist (WAY100635) enhanced the NK1-5-HT1A receptor coimmunoprecipitation along with the depigmentary response. SP and WAY100635 cooperation elicited activation of a signaling cascade (the extracellular, regulated protein kinase p-JNK signaling pathway) and inhibition of p70S6K1 phosphorylation and greatly reduced melanin production in vitro and in vivo in mice and zebrafish. Moreover, the SP-induced depigmentation response did not be occur in 5-htr1aa(+/-)zebrafish embryos. Taken together, the results of our systemic study increases our knowledge of the roles of NK1R and 5-HT1AR in melanogenesis and provides possible, novel therapeutic strategies for treatment of skin hypo/hyperpigmentation. |
| WOS关键词 | RESONANCE ENERGY-TRANSFER ; CELL-SURFACE EXPRESSION ; SUBSTANCE-P ; SEROTONIN RECEPTORS ; NEUROKININ-1 RECEPTOR ; MELANIN SYNTHESIS ; TRYPTOPHAN-HYDROXYLASE ; ENDOPLASMIC-RETICULUM ; TRANSCRIPTION FACTOR ; SKIN PIGMENTATION |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000432546000025 |
| 出版者 | FEDERATION AMER SOC EXP BIOL |
| 资助机构 | Science and Technology Plan Projects in Qinghai Province(2015-ZJ-733) ; Science and Technology Plan Projects in Xinjiang(2014AB043) ; National Natural Science Foundation of China(81603216) ; CMA-L'OREAL China Skin/Hair Grant(S2017140917) ; One Hundred Person Project of the Chinese Academy of Sciences, Applied Basic Research Programs of Qinghai Province(Y229461211) ; Prospective Joint Research Project of Jiangsu Province(BY2016078-02) |
| 源URL | [http://ir.nwipb.ac.cn/handle/363003/13804]  |
| 专题 | 西北高原生物研究所_中国科学院西北高原生物研究所 |
| 通讯作者 | Shang, Jing |
| 作者单位 | 1.Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA 2.Xinjiang Med Univ, Affiliated Tumor Hosp, Urumqi, Peoples R China 3.Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Key Lab Tibetan Med Pharmacol & Safety Ev, Xining, Qinghai, Peoples R China 4.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Nanjing, Jiangsu, Peoples R China 5.China Pharmaceut Univ, Jiangsu Key Lab Tradit Chinese Med TCM Evaluat &, Nanjing, Jiangsu, Peoples R China 6.China Pharmaceut Univ, Dept Pharmacol, Nanjing, Jiangsu, Peoples R China 7.China Pharmaceut Univ, State Key Lab Nat Med, Nanjing, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shang, Jing,He, Ling,Jin, Yu,et al. NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis[J]. FASEB JOURNAL,2018,32(6):3193-3214. |
| APA | Shang, Jing.,He, Ling.,Jin, Yu.,Liu, Meng.,Xia, Zhenjiang.,...&Wu, Huali.(2018).NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis.FASEB JOURNAL,32(6),3193-3214. |
| MLA | Shang, Jing,et al."NK 1R/5-HT1AR interaction is related to the regulation of melanogenesis".FASEB JOURNAL 32.6(2018):3193-3214. |
入库方式： OAI收割
来源：西北高原生物研究所
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