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|Title:||Activation of mitochondrial transient receptor potential vanilloid 1 channel contributes to microglial migration.|
|Authors:||Miyake, Takahito |
|Author's alias:||白川, 久志|
|Abstract:||Microglia, the resident immune cells in the brain, survey the environment of the healthy brain. Microglial migration is essential for many physiological and pathophysiological processes. Although microglia express some members of the transient receptor potential (TRP) channel family, there is little knowledge regarding the physiological roles of TRP channels in microglia. Here, we explored the role of TRP vanilloid 1 (TRPV1), a channel opened by capsaicin, heat, protons, and endovanilloids, in microglia. We found that application of capsaicin induced concentration-dependent migration in microglia derived from wild-type mice but not in those derived from TRPV1 knockout (TRPV1-KO) mice. Capsaicin-induced microglial migration was significantly inhibited by co-application of the TRPV1 blocker SB366791 and the Ca(2+) chelator BAPTA-AM. Using RT-PCR and immunocytochemistry, we validated that TRPV1 was expressed in microglia. Electrophysiological recording, intracellular Ca(2+) imaging, and immunocytochemistry indicated that TRPV1 was localized primarily in intracellular organelles. Treatment with capsaicin induced an increase in intramitochondrial Ca(2+) concentrations and mitochondrial depolarization. Furthermore, microglia derived from TRPV1-KO mice showed delayed Ca(2+) efflux compared with microglia derived from wild-type mice. Capsaicin-induced microglial migration was inhibited by membrane-permeable antioxidants and MAPK inhibitors, suggesting that mitochondrial TRPV1 activation induced Ca(2+) -dependent production of ROS followed by MAPK activation, which correlated with an augmented migration of microglia. Moreover, a mixture of three endovanilloids augmented microglial migration via TRPV1 activation. Together, these results indicate that mitochondrial TRPV1 plays an important role in inducing microglial migration. Activation of TRPV1 triggers an increase in intramitochondrial Ca(2+) concentration and following depolarization of mitochondria, which results in mtROS production, MAPK activation, and enhancement of chemotactic activity in microglia.|
|Description:||Article first published online: 23 MAY 2015|
|Rights:||This is the peer reviewed version of the following article: Miyake, T., Shirakawa, H., Nakagawa, T. and Kaneko, S. (2015), Activation of mitochondrial transient receptor potential vanilloid 1 channel contributes to microglial migration. Glia, 63: 1870–18, which has been published in final form at http://dx.doi.org/10.1002/glia.22854. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.|
The full-text file will be made open to the public on 23 MAY 2016 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
|Appears in Collections:||Journal Articles|
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