Mitochondrial reactive oxygen species(mROS)that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities.Here,we explored whether mROS overproduction induces ...Mitochondrial reactive oxygen species(mROS)that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities.Here,we explored whether mROS overproduction induces itch through transient receptor potential canonical 3(TRPC3),which is sensitive to ROS.Intradermal injection of antimycin A(AA),a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction,produced robust scratching behavior in naïve mice,which was suppressed by MitoTEMPO,a mitochondria-selective ROS scavenger,and Pyr10,a TRPC3-specific blocker,but not by blockers of TRPA1 or TRPV1.AA activated subsets of trigeminal ganglion neurons and also induced inward currents,which were blocked by MitoTEMPO and Pyr10.Besides,dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10,and also by resveratrol,an antioxidant.Taken together,our results suggest that mROS elicit itch through TRPC3,which may underlie chronic itch,representing a potential therapeutic target for chronic itch.展开更多
基金supported by the National Research Foundation(NRF)funded by the Ministry of Science,ICT&Future Planning(NRF-2018R1A5A2024418 and NRF-2021R1A2C3003334)the Basic Science Research Program through the NRF funded by the Ministry of Education(NRF-2020R1I1A1A01068037).
文摘Mitochondrial reactive oxygen species(mROS)that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities.Here,we explored whether mROS overproduction induces itch through transient receptor potential canonical 3(TRPC3),which is sensitive to ROS.Intradermal injection of antimycin A(AA),a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction,produced robust scratching behavior in naïve mice,which was suppressed by MitoTEMPO,a mitochondria-selective ROS scavenger,and Pyr10,a TRPC3-specific blocker,but not by blockers of TRPA1 or TRPV1.AA activated subsets of trigeminal ganglion neurons and also induced inward currents,which were blocked by MitoTEMPO and Pyr10.Besides,dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10,and also by resveratrol,an antioxidant.Taken together,our results suggest that mROS elicit itch through TRPC3,which may underlie chronic itch,representing a potential therapeutic target for chronic itch.
