借助辣椒素受体TRPV1迎接新机遇：mTOR、AMPK与促红细胞生成素
Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin.
作者信息
Maiese Kenneth
机构信息
Cellular and Molecular Signaling. United States.
出版信息
Curr Neurovasc Res. 2017;14(2):184-189. doi: 10.2174/1567202614666170313105337.
BACKGROUND
Transient receptor potential (TRP) channels are a superfamily of ion channels termed after the trp gene in Drosophila that are diverse in structure and control a wide range of biological functions including cell development and growth, thermal regulation, and vascular physiology. Of significant interest is the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, also known as the capsaicin receptor and the vanilloid receptor 1, that is a non-selective cation channel sensitive to a host of external stimuli including capsaicin and camphor, venoms, acid/basic pH changes, and temperature.
METHODS
Given the multiple modalities that TRPV1 receptors impact in the body, we examined and discussed the role of these receptors in vasomotor control, metabolic disorders, cellular injury, oxidative stress, apoptosis, autophagy, and neurodegenerative disorders and their overlap with other signal transduction pathways that impact trophic factors.
RESULTS
Surprisingly, TRPV1 receptors do not rely entirely upon calcium signaling to affect cellular biology, but also have a close relationship with the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and protein kinase B (Akt) that have roles in pain sensitivity, stem cell development, cellular survival, and cellular metabolism. These pathways with TRPV1 converge in the signaling of growth factors with recent work highlighting a relationship with erythropoietin (EPO). Angiogenesis and endothelial tube formation controlled by EPO requires, in part, the activation of TRPV1 receptors in conjunction with Akt and AMPK pathways.
CONCLUSION
TRPV1 receptors could prove to become vital to target disorders of vascular origin and neurodegeneration. Broader and currently unrealized implementations for both EPO and TRPV1 receptors can be envisioned for for the development of novel therapeutic strategies in multiple systems of the body.
背景
瞬时受体电位（TRP）通道是一类离子通道超家族，以果蝇中的trp基因命名，其结构多样，控制着广泛的生物学功能，包括细胞发育与生长、体温调节及血管生理学。其中备受关注的是瞬时受体电位阳离子通道亚家族V成员1（TRPV1）受体，也被称为辣椒素受体和香草酸受体1，它是一种对多种外部刺激敏感的非选择性阳离子通道，这些刺激包括辣椒素、樟脑、毒液、酸碱pH变化及温度。
方法
鉴于TRPV1受体在体内影响多种生理过程，我们研究并讨论了这些受体在血管运动控制、代谢紊乱、细胞损伤、氧化应激、细胞凋亡、自噬及神经退行性疾病中的作用，以及它们与影响营养因子的其他信号转导途径的重叠情况。
结果
令人惊讶的是，TRPV1受体并不完全依赖钙信号来影响细胞生物学，还与雷帕霉素作用靶点（mTOR）、AMP激活的蛋白激酶（AMPK）和蛋白激酶B（Akt）密切相关，这些在疼痛敏感性、干细胞发育、细胞存活及细胞代谢中发挥作用。TRPV1与这些途径在生长因子信号传导中汇聚，近期研究突出了其与促红细胞生成素（EPO）的关系。EPO控制的血管生成和内皮管形成部分需要TRPV1受体与Akt和AMPK途径共同激活。
结论
TRPV1受体可能对血管源性疾病和神经退行性疾病的靶向治疗至关重要。对于EPO和TRPV1受体，可设想在身体多个系统开发新治疗策略方面有更广泛且目前尚未实现的应用。
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