title: Stress hormone potentiates Zn(2+)-induced neurotoxicity via TRPM7 channel in dopaminergic neuron.
abstract: Zinc toxicity is one of the key factors responsible for the neuronal injuries associated with various neurological conditions. Zinc accumulation in some cells is accompanied by the increase of blood stress hormone levels, which might indicate a functional connection between stress and zinc toxicity. However, the cellular mechanism for the effect of stress on zinc toxicity is not known. Recently, it was reported that the zinc permeable transient receptor potential melastatin 7 (TRPM7) channel may represent a novel target for neurological disorders where zinc toxicity plays an important role. To investigate the effect of stress hormone on zinc-induced cell death, neuroblastoma SH-SY5Y cells were pretreated with urocortin, a corticotropin releasing factor (CRF)-related peptide. Urocortin potentiated zinc-induced cell death at μM range of extracellular zinc concentrations. It significantly increased TRPM7 channel expression, and zinc influx into cytosol. Moreover, application of TRPM7 channel blockers and RNA interference of TRPM7 channel expression attenuated the zinc-induced cell death in urocortin-pretreated cells, indicating that TRPM7 channel may serve as a zinc influx pathway. These results suggest that TRPM7 channel may play a critical role for zinc toxicity associated with stress.
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Yonjung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Hyun Geun
authors.initials: HG
authors.lastname: Oh
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Cho
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Oh-Hoon
authors.initials: OH
authors.lastname: Kwon
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Myoung Kyu
authors.initials: MK
authors.lastname: Park
authors.affiliation: Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea. Electronic address: schung@skku.edu.
authors.forename: Sungkwon
authors.initials: S
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D009498:Neurotoxins / Q000008:administration & dosage; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000378:metabolism*; D054832:Urocortins / Q000008:administration & dosage*; D015032:Zinc / Q000633:toxicity*
chemical_list: D009498:Neurotoxins; D050053:TRPM Cation Channels; D054832:Urocortins; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D015032:Zinc
keywords: Neurotoxicity; Stress hormone; TRPM7 channel; Zn(2+)