Wang Bin, Yang Guokun, Liu Quan, Qin Jingkai, Xu Yongjiang, Li Wensheng, Liu Xuezhou, Shi Bao
Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China; Laboratory for Marine Fisheries and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.
State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, South China Sea Bio-Resource Exploitation and Collaborative Innovation Center, Research Institute of Sun Yat-Sen University in Shen Zhen, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Peptides. 2017 Sep;95:62-67. doi: 10.1016/j.peptides.2017.07.014. Epub 2017 Jul 25.
Kisspeptin (Kiss) acts as a positive regulator of reproduction by acting on gonadotropes and gonadotropin-releasing hormone (GnRH) neurons. Despite its functional significance, the intricate web of intracellular signal transduction pathways in response to Kiss is still far from being fully understood in teleosts. Accordingly, we investigated the molecular mechanism of Kiss action and its possible interaction with LPXRFa signaling in this study. In vitro functional analysis revealed that synthetic tongue sole Kiss2 decapeptide increased the cAMP responsive element-dependent luciferase (CRE-luc) activity in COS-7 cells transfected with its cognate receptor, while this stimulatory effect was markedly reduced by two inhibitors of the adenylate cyclase (AC)/protein kinase A (PKA) pathway. Similarly, Kiss2 also significantly stimulated serum responsive element-dependent luciferase (SRE-luc) activity, whereas this stimulatory effect was evidently attenuated by two inhibitors of the phospholipase C (PLC)/protein kinase C (PKC) pathway. In addition, LPXRFa-2 suppressed Kiss2-elicited CRE-luc activity in a dose-dependent manner. Taken together, Kiss2 utilizes both AC/PKA and PLC/PKC pathways to exert its functions via its cognate receptor and LPXRFa may antagonize the action of Kiss2 by inhibiting kisspeptin signaling. As far as we know, this study is the first to characterize the half-smooth tongue sole kisspeptin and LPXRFa signaling pathway in COS-7 cells transfected with their cognate receptors and provides novel information on the interaction between LPXRFa system and kisspeptin system in teleosts.
亲吻素（Kiss）通过作用于促性腺激素细胞和促性腺激素释放激素（GnRH）神经元，作为生殖的正向调节因子。尽管其具有功能意义，但在硬骨鱼中，响应Kiss的复杂细胞内信号转导途径网络仍远未被完全理解。因此，在本研究中，我们调查了Kiss作用的分子机制及其与LPXRFa信号传导的可能相互作用。体外功能分析表明，合成的舌鳎Kiss2十肽增加了转染其同源受体的COS-7细胞中cAMP反应元件依赖性荧光素酶（CRE-luc）的活性，而这种刺激作用被腺苷酸环化酶（AC）/蛋白激酶A（PKA）途径的两种抑制剂显著降低。同样，Kiss2也显著刺激血清反应元件依赖性荧光素酶（SRE-luc）的活性，而这种刺激作用被磷脂酶C（PLC）/蛋白激酶C（PKC）途径的两种抑制剂明显减弱。此外，LPXRFa-2以剂量依赖性方式抑制Kiss2诱导的CRE-luc活性。综上所述，Kiss2通过其同源受体利用AC/PKA和PLC/PKC途径发挥其功能，并且LPXRFa可能通过抑制亲吻素信号传导来拮抗Kiss2的作用。据我们所知，本研究首次在转染其同源受体的COS-7细胞中表征了半滑舌鳎亲吻素和LPXRFa信号通路，并提供了关于硬骨鱼中LPXRFa系统与亲吻素系统之间相互作用的新信息。
