Rab7-a novel redox target that modulates inflammatory pain processing.

Autor: Kallenborn-Gerhardt W; Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.; Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany., Möser CV; Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany., Lorenz JE; Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany., Steger M; Functional Proteomics, SFB815 Core Unit, Goethe University, Frankfurt am Main, Germany., Heidler J; Functional Proteomics, SFB815 Core Unit, Goethe University, Frankfurt am Main, Germany., Scheving R; Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany., Petersen J; Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.; Institute of Pharmacology and Toxicology, ZBAF, Witten/Herdecke University, Witten, Germany., Kennel L; Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany., Flauaus C; Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany., Lu R; Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.; Institute of Pharmacology and Toxicology, ZBAF, Witten/Herdecke University, Witten, Germany., Edinger AL; Developmental and Cell Biology, University of California, Irvine, CA, USA., Tegeder I; Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany., Geisslinger G; Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.; Fraunhofer Institute for Molecular Biology and Applied Ecology-Project Group Translational Medicine and Pharmacology (IME-TMP), Frankfurt am Main, Germany., Heide H; Functional Proteomics, SFB815 Core Unit, Goethe University, Frankfurt am Main, Germany., Wittig I; Functional Proteomics, SFB815 Core Unit, Goethe University, Frankfurt am Main, Germany., Schmidtko A; Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.; Institute of Pharmacology and Toxicology, ZBAF, Witten/Herdecke University, Witten, Germany.
Jazyk: angličtina
Zdroj: Pain [Pain] 2017 Jul; Vol. 158 (7), pp. 1354-1365.
DOI: 10.1097/j.pain.0000000000000920
Abstrakt: Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice. Prevention of Rab7 oxidation by replacement of the redox-sensing thiols modulates its GTPase activity. Immunofluorescence studies revealed Rab7 expression to be enriched in central terminals of sensory neurons. Knockout mice lacking Rab7 in sensory neurons showed normal responses to noxious thermal and mechanical stimuli; however, their pain behavior during inflammatory pain and in response to ROS donors was reduced. The data suggest that redox-dependent changes in Rab7 activity modulate inflammatory pain sensitivity.
Databáze: MEDLINE
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