title: Essential role of mitochondrial permeability transition in vanilloid receptor 1-dependent cell death of sensory neurons.
abstract: Capsaicin causes pain by activating VR1, a cloned capsaicin receptor, in sensory neurons. After the initial excitatory responses, capsaicin produces prolonged analgesia, presumably because of the neurotoxic effect that leads to the death of sensory neurons. However, the mechanism underlying capsaicin-induced cell death of sensory neurons is not known. Here we report that capsaicin induces cell death in VR1-expressing sensory neurons and VR1-transfected human embryonic kidney cells. Cell death of sensory neurons induced by capsaicin is accompanied by DNA fragmentation, TUNEL staining, and shrinkage of the nucleus in a caspase-dependent manner, indicating the apoptotic nature of the cell death. Mitochondrial permeability transition is likely to be a major component of capsaicin-induced cell death because bonkrekic acid and cyclosporin A, inhibitors of mitochondrial permeability transition, block this cell death. These results imply that capsaicin induces mitochondrial dysfunction in VR1-expressing cells, leading to apoptotic cell death, which is a well-known neurotoxic effect of capsaicin.
authors.affiliation: The Sensory Research Center, National Creative Research Initiatives, Seoul National University, College of Pharmacy, Kwanak-Gu, Shinlim 9-dong, Seoul 151-742, South Korea.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Jieun
authors.initials: J
authors.lastname: Shin
authors.forename: Byung-Moon
authors.initials: BM
authors.lastname: Kim
authors.forename: Myeong-Hyeon
authors.initials: MH
authors.lastname: Wang
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Jang
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
authors.forename: Uhtaek
authors.initials: U
authors.lastname: Oh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D010146:Pain / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D010539:Permeability / Q000187:drug effects; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D009498:Neurotoxins; D011955:Receptors, Drug; D016572:Cyclosporine; D002211:Capsaicin