Blue light (λ=453 nm) nitric oxide dependently induces β-endorphin production of human skin keratinocytes in-vitro and increases systemic β-endorphin levels in humans in-vivo
Blue light (λ=453 nm) nitric oxide dependently induces β-endorphin production of human skin keratinocytes in-vitro and increases systemic β-endorphin levels in humans in-vivo
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DOI：
10.1016/j.freeradbiomed.2019.09.022
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发表时间：
2019-12-01
影响因子：
7.4
通讯作者：
Suschek, Christoph V.
中科院分区：
文献类型：
--
作者：
Albers, Isabel;Zernickel, Erika;Suschek, Christoph V.
β-内啡肽对情绪、免疫功能、疼痛管理、奖励效应和行为稳定性发挥广泛的生理活性。β-内啡肽在中枢和外周神经系统内的某些神经元中产生，但也在皮肤中产生，特别是响应于紫外线辐射。在本研究中，我们研究了λ = 453 nm（BL）的可见蓝光对体外原代人皮肤角质形成细胞（hKC）产生β-内啡肽以及全身暴露受试者体内形成全身β-内啡肽的影响。我们发现，BL照射显着增强角质形成细胞β-内啡肽的生产的hKC文化，以及全身β-内啡肽浓度在光暴露的健康受试者。有趣的是，在hKC培养物中，β-内啡肽形成的升高被显著增加的非酶促产生的一氧化氮（NO）水平所抑制，而BL暴露受试者的全身β-内啡肽值升高伴随着生物活性NO衍生物的全身浓度增强。这些发现指出NO在所观察到的BL诱导效应的分子机制中的关键作用，并且确实，外源性应用NO能够显著增强hKC培养物中β-内啡肽的产生。因此，我们发现BL诱导的体内全身β-内啡肽浓度增加可以通过包括1.）BL驱动的NO在暴露的皮肤组织中的非酶促形成，2.）以生物活性亚硝基化合物的形式产生的NO的全身分布，3.）随后在表皮角质形成细胞中NO依赖性诱导β-内啡肽合成，和4.）可能也是中枢和外周神经系统内专门神经元中β-内啡肽合成的NO依赖性调节。
beta-Endorphin exerts a broad spectrum of physiological activity on mood, immune functions, pain management, reward effects, and behavioral stability. beta-Endorphin is produced in certain neurons within the central and peripheral nervous system but also in the skin, especially in response to ultraviolet radiation. In the present study we have investigated the impact of visible blue light at lambda = 453 nm (BL) on beta-endorphin production of primary human skin keratinocytes (hKC) in-vitro as well as on systemic beta-endorphin formation of whole-body exposed subjects in-vivo. We found that BL irradiation significantly enhanced both keratinocytic beta-endorphin production of hKC cultures as well as systemic beta-endorphin concentrations in light exposed healthy subjects. Interestingly, in hKC cultures elevated beta-endorphin formation was paralleled by significantly increased levels of non-enzymatically generated nitric oxide (NO), whereas elevated systemic beta-endorphin values of BL-exposed subjects were accompanied by enhanced systemic concentration of bioactive NO-derivates. These findings point to a pivotal role of NO in the molecular mechanism of the observed BL-induced effects, and indeed, exogenously applied NO was able to significantly enhance beta-endorphin production in hKC cultures. Thus, our finding of BL-induced increases in systemic beta-endorphin concentration in-vivo can be plausibly explained by an event sequence comprising 1.) BL-driven non-enzymatic formation of NO in the exposed skin tissue, 2.) systemic distribution of cutaneously produced NO in the form of bioactive nitroso compounds, 3.) a subsequent NO-dependent induction of beta-endorphin synthesis in epidermal keratinocytes, and 4.) probably also a NO-dependent modulation of beta-endorphin synthesis in specialized neurons within the central and peripheral nervous system.