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Characterization of serotonin and N-acetylserotonin systems in the human epidermis and skin cells.
Journal of Pineal Research ( IF 10.3 ) Pub Date : 2019-11-26 , DOI: 10.1111/jpi.12626
Andrzej T Slominski 1, 2 , Tae-Kang Kim 1 , Konrad Kleszczyński 3 , Igor Semak 4 , Zorica Janjetovic 1 , Trevor Sweatman 5 , Cezary Skobowiat 6 , Jeffery D Steketee 5 , Zongtao Lin 7 , Arnold Postlethwaite 8, 9 , Wei Li 7 , Russel J Reiter 10 , Desmond J Tobin 11
Affiliation  

Tryptophan hydroxylase (TPH) activity was detected in cultured epidermal melanocytes and dermal fibroblasts with respective Km of 5.08 and 2.83 mM and Vmax of 80.5 and 108.0 µmol/min. Low but detectable TPH activity was also seen in cultured epidermal keratinocytes. Serotonin and/or its metabolite and precursor to melatonin, N-acetylserotonin (NAS), were identified by LC/MS in human epidermis and serum. Endogenous epidermal levels were 113.18 ± 13.34 and 43.41 ± 12.45 ng/mg protein for serotonin (n = 8/8) and NAS (n = 10/13), respectively. Their production was independent of race, gender, and age. NAS was also detected in human serum (n = 13/13) at a concentration 2.44 ± 0.45 ng/mL, while corresponding serotonin levels were 295.33 ± 17.17 ng/mL (n = 13/13). While there were no differences in serum serotonin levels, serum NAS levels were slightly higher in females. Immunocytochemistry studies showed localization of serotonin to epidermal and follicular keratinocytes, eccrine glands, mast cells, and dermal fibrocytes. Endogenous production of serotonin in cultured melanocytes, keratinocytes, and dermal fibroblasts was modulated by UVB. In conclusion, serotonin and NAS are produced endogenously in the epidermal, dermal, and adnexal compartments of human skin and in cultured skin cells. NAS is also detectable in human serum. Both serotonin and NAS inhibited melanogenesis in human melanotic melanoma at concentrations of 10-4 -10-3 M. They also inhibited growth of melanocytes. Melanoma cells were resistant to NAS inhibition, while serotonin inhibited cell growth only at 10-3 M. In summary, we characterized a serotonin-NAS system in human skin that is a part of local neuroendocrine system regulating skin homeostasis.

中文翻译:

人表皮和皮肤细胞中5-羟色胺和N-乙酰5-羟色胺系统的表征。

在培养的表皮黑素细胞和真皮成纤维细胞中检测到色氨酸羟化酶(TPH)活性,其Km分别为5.08和2.83 mM,Vmax为80.5和108.0 µmol / min。在培养的表皮角质形成细胞中也观察到了较低但可检测到的TPH活性。通过LC / MS在人表皮和血清中鉴定出5-羟色胺和/或其代谢产物以及褪黑激素的前体N-乙酰5-羟色胺(NAS)。血清素(n = 8/8)和NAS(n = 10/13)的内源性表皮水平分别为113.18±13.34和43.41±12.45 ng / mg蛋白。他们的生产与种族,性别和年龄无关。还以2.44±0.45 ng / mL的浓度在人血清中检测到NAS(n = 13/13),而相应的血清素水平为295.33±17.17 ng / mL(n = 13/13)。虽然血清血清素水平没有差异,女性血清NAS水平略高。免疫细胞化学研究表明,血清素定位于表皮和滤泡角质形成细胞,外分泌腺,肥大细胞和真皮纤维细胞。UVB调节培养的黑素细胞,角质形成细胞和真皮成纤维细胞中5-羟色胺的内源性产生。总之,5-羟色胺和NAS是在人类皮肤的表皮,真皮和附件隔室内以及培养的皮肤细胞中内源性产生的。在人血清中也可检测到NAS。血清素和NAS均以10-4 -10-3 M的浓度抑制人黑素瘤黑素瘤中的黑素生成。它们还抑制黑素细胞的生长。黑色素瘤细胞对NAS抑制有抵抗力,而血清素仅在10-3 M时抑制细胞生长。
更新日期:2019-12-21
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