title: Electrical stimulation induces calcium-dependent release of NGF from cultured Schwann cells.
abstract: Production of nerve growth factor (NGF) from Schwann cells (SCs) progressively declines in the distal stump, if axonal regeneration is staggered across the suture site after peripheral nerve injuries. This may be an important factor limiting the outcome of nerve injury repair. Thus far, extensive efforts are devoted to modulating NGF production in cultured SCs, but little has been achieved. In the present in vitro study, electrical stimulation (ES) was attempted to stimulate cultured SCs to release NGF. Our data showed that ES was capable of enhancing NGF release from cultured SCs. An electrical field (1 Hz, 5 V/cm) caused a 4.1-fold increase in NGF release from cultured SCs. The ES-induced NGF release is calcium dependent. Depletion of extracellular or/and intracellular calcium partially/ completely abolished the ES-induced NGF release. Further pharmacological interventions showed that ES induces calcium influx through T-type voltage-gated calcium channels and mobilizes calcium from 1, 4, 5-trisphosphate-sensitive stores and caffeine/ryanodine-sensitive stores, both of which contributed to the enhanced NGF release induced by ES. In addition, a calcium-triggered exocytosis mechanism was involved in the ES-induced NGF release from cultured SCs. These findings show the feasibility of using ES in stimulating SCs to release NGF, which holds great potential in promoting nerve regeneration by enhancing survival and outgrowth of damaged nerves, and is of great significance in nerve injury repair and neuronal tissue engineering.
authors.affiliation: Department of Spine Surgery, Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Huang
authors.forename: Zhengxu
authors.initials: Z
authors.lastname: Ye
authors.forename: Xueyu
authors.initials: X
authors.lastname: Hu
authors.forename: Lei
authors.initials: L
authors.lastname: Lu
authors.forename: Zhuojing
authors.initials: Z
authors.lastname: Luo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D019274:Botulinum Toxins, Type A / Q000494:pharmacology; D019256:Cadmium Chloride / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004963:Estrenes / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D020748:Mibefradil / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002614:Chelating Agents; D003572:Cytochalasins; D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011500:Protein Synthesis Inhibitors; D011760:Pyrrolidinones; D009418:S100 Proteins; D050257:Tubulin Modulators; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C031218:cytochalasin A; D020748:Mibefradil; D002110:Caffeine; D004533:Egtazic Acid; D020932:Nerve Growth Factor; D019274:Botulinum Toxins, Type A; D009355:Neomycin; D019256:Cadmium Chloride; D015739:Nocodazole; D002118:Calcium