Zhou Jun, Lv Xiao-Hui, Fan Jun-Juan, Dang Li-Yun, Dong Kun, Gao Bo, Song Ao-Qi, Wu Wen-Ning
Department of Pharmacy, Xi'an Chest Hospital, Shaanxi University of Chinese Medicine, Xi'an, China.
Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Anhui Medical University, Hefei, China.
Front Pharmacol. 2018 Aug 21;9:966. doi: 10.3389/fphar.2018.00966. eCollection 2018.
Hydrogen sulfide (HS) is an endogenous gaseous molecule and plays important biological and neurochemical roles in many processes such as the neural activity and immunity. The arcuate nucleus (ARC) of hypothalamus is a control center for appetite and energy metabolism. AMPK is a gage kinase in the monitoring of energy status and regulation of energy metabolism, and it can be activated by HS via CaMKKβ/AMPK pathway. But the role of HS in ARC and appetite has not been reported. Here we studied the orexigenic effect of HS and the mechanisms by means of GYY4137, a water soluble and slow-releasing donor of HS, and protein sulfur-sulfhydrylation analysis. We demonstrated that GYY4137-derived HS increased food intake of mice, augmented the production of neuropeptide Y (NPY), and elevated the protein sulfur-sulfhydrylation level and the activation of AMPK and CaMKKβ in ARC. Blocking sulfur-sulfhydrylation with DTT eliminated GYY4137-induced activation of AMPK and CaMKKβ. DTT and preventing AMPK activation in ARC with Compound C and Ara-A could both attenuate the orexigenic effect of GYY4137. These findings suggest that HS enhances appetite through protein sulfur-sulfhydrylation and the activation of AMPK and NPY function in ARC.
硫化氢（HS）是一种内源性气体分子，在神经活动和免疫等许多过程中发挥着重要的生物学和神经化学作用。下丘脑弓状核（ARC）是食欲和能量代谢的控制中心。AMPK是监测能量状态和调节能量代谢的一种关键激酶，它可通过CaMKKβ/AMPK途径被HS激活。但HS在ARC和食欲方面的作用尚未见报道。在此，我们借助GYY4137（一种水溶性且缓释的HS供体）和蛋白质硫-巯基化分析，研究了HS的致食欲作用及其机制。我们证明，GYY4137衍生的HS增加了小鼠的食物摄入量，增强了神经肽Y（NPY）的产生，并提高了ARC中蛋白质硫-巯基化水平以及AMPK和CaMKKβ的活性。用二硫苏糖醇（DTT）阻断硫-巯基化消除了GYY4137诱导的AMPK和CaMKKβ激活。DTT以及用化合物C和阿糖腺苷（Ara-A）抑制ARC中的AMPK激活，均可减弱GYY4137的致食欲作用。这些发现表明，HS通过蛋白质硫-巯基化以及ARC中AMPK的激活和NPY功能增强食欲。
