title: Involvement of volume-activated chloride channels in H2O 2 preconditioning against oxidant-induced injury through modulating cell volume regulation mechanisms and membrane permeability in PC12 cells.
abstract: The functions of chloride channels in preconditioning-induced cell protection remain unclear. In this report, we show that the volume-activated chloride channels play a key role in hydrogen peroxide (H2O2) preconditioning-induced cell protection in pheochromocytoma PC12 cells. The preconditioning with 100 μM H2O2 for 90 min protected the cells from injury induced by long period exposure to 300 μM H2O2. The protective effect was attenuated by pretreatment with the chloride channel blockers, 5-nitro-2-3-phenylpropylamino benzoic acid (NPPB) and tamoxifen. H2O2 preconditioning directly activated a chloride current, which was moderately outward-rectified and sensitive to the chloride channel blockers and hypertonicity-induced cell shrinkage. H2O2 preconditioning functionally up-regulated the activities of volume-activated chloride channels and enhanced the regulatory volume decrease when exposure to extracellular hypotonic challenges. In addition, acute application of H2O2 showed distinctive actions on cell volume and membrane permeability in H2O2 preconditioned cells. In H2O2 preconditioned cells, acute application of 300 μM H2O2 first promptly induced a decrease of cell volume and enhancement of cell membrane permeability, and then, cell volume was maintained at a relatively stable level and the facilitation of membrane permeability was reduced. Conversely, in control cells, 300 μM H2O2 induced a slow but persistent apoptotic volume decrease (AVD) and facilitation of membrane permeability. H2O2 preconditioning also significantly up-regulated the expression of ClC-3 protein, the molecular candidate of the volume-activated chloride channel. These results suggest that H2O2 preconditioning can enhance the expression and functional activities of volume-activated chloride channels, thereby modulate cell volume and cell membrane permeability, which may contribute to neuroprotection against oxidant-induced injury.
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.forename: Wanhong
authors.initials: W
authors.lastname: Zuo
authors.forename: Haifeng
authors.initials: H
authors.lastname: Yang
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Hai
authors.initials: H
authors.lastname: Luo
authors.forename: Dong
authors.initials: D
authors.lastname: Ye
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.forename: Jianwen
authors.initials: J
authors.lastname: Mao
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Feng
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006690:Bisbenzimidazole / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects*; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004396:Coloring Agents / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007038:Hypotonic Solutions / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D009579:Nitrobenzoates / Q000494:pharmacology; D016877:Oxidants / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats; D013312:Stress, Physiological / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018118:Chloride Channels; C115376:ClC-3 channel; D004396:Coloring Agents; D007038:Hypotonic Solutions; D009579:Nitrobenzoates; D016877:Oxidants; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D004247:DNA; D006861:Hydrogen Peroxide; D006690:Bisbenzimidazole
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