Mori Yasuo, Takahashi Nobuaki, Kurokawa Tatsuki, Kiyonaka Shigeki
Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University.
Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):464-482. doi: 10.2183/pjab.93.028.
Transient Receptor Potential (TRP) proteins form cation channels characterized by a wide variety of activation triggers. Here, we overview a group of TRP channels that respond to reactive redox species to transduce physiological signals, with a focus on TRPA1 and its role in oxygen physiology. Our systematic evaluation of oxidation sensitivity using cysteine-selective reactive disulphides with different redox potentials reveals that TRPA1 has the highest sensitivity to oxidants/electrophiles among the TRP channels, which enables it to sense O. Proline hydroxylation by O-dependent hydroxylases also regulates the O-sensing function by inhibiting TRPA1 in normoxia; TRPA1 is activated by hypoxia through relief from the inhibition and by hyperoxia through cysteine oxidation that overrides the inhibition. TRPA1 enhances neuronal discharges induced by hyperoxia and hypoxia in the vagus to underlie respiratory adaptation to changes in O availability. This importance of TRPA1 in non-carotid body O sensors can be extended to the universal significance of redox-sensitive TRP channels in O adaptation.
瞬时受体电位（TRP）蛋白形成阳离子通道，其特征是具有多种激活触发因素。在此，我们概述了一组对活性氧化还原物质作出反应以转导生理信号的TRP通道，重点关注TRPA1及其在氧生理学中的作用。我们使用具有不同氧化还原电位的半胱氨酸选择性反应性二硫化物对氧化敏感性进行的系统评估表明，TRPA1在TRP通道中对氧化剂/亲电试剂具有最高的敏感性，这使其能够感知O。依赖O的羟化酶进行的脯氨酸羟化也通过在常氧下抑制TRPA1来调节O感知功能；TRPA1在缺氧时通过解除抑制而被激活，在高氧时通过半胱氨酸氧化而被激活，这种氧化作用会覆盖抑制作用。TRPA1增强了迷走神经中高氧和缺氧诱导的神经元放电，从而成为呼吸适应氧可用性变化的基础。TRPA1在非颈动脉体氧传感器中的这种重要性可以扩展到氧化还原敏感的TRP通道在氧适应中的普遍意义。
