title: Effect of hydrogen sulfide on intracellular calcium homeostasis in neuronal cells.
abstract: Hydrogen sulfide (H(2)S) is now known as a new biological mediator. In the present study, the effects of H(2)S on intracellular calcium ([Ca(2+)](i)) in neuronal SH-SY5Y cells was investigated. In SH-SY5Y neuronal cells, NaHS, a H(2)S donor, concentration-dependently increased [Ca(2+)](i). The H(2)S-induced Ca(2+) elevation was significantly attenuated by EGTA-treated calcium-free Krebs' solution. This elevation was also reduced by antagonists of L-type (verapamil and nifedipine), T-type (mibefradil) calcium channels and N-methyl-d-aspartate receptor (MK-801, AP-5 and ifenprodil). A 90% reduction in H(2)S-induced [Ca(2+)](i) elevation was found in cells pretreated with combination of all three kinds of inhibitors. Depletion of intracellular Ca(2+) store with thapsigargin or cyclopiazonic acid or blockade of ryanodine receptor with ruthenium red significantly attenuated the effect of H(2)S on [Ca(2+)](i). Inhibition of protein kinase A (PKA), phospholipase C (PLC) and protein kinase C (PKC) suppressed the H(2)S-elevated [Ca(2+)](i), suggesting that H(2)S may regulate [Ca(2+)](i) via both PKA and PLC/PKC pathways. In conclusion, it was found in this study that H(2)S increased [Ca(2+)](i) in SH-SY5Y neuronal cells by increasing Ca(2+) influx via plasma membrane and in turn releasing calcium from intracellular calcium store. The findings in the present study provide the direct evidence that H(2)S may serve as a neuromodulator.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore.
authors.forename: Qian Chen
authors.initials: QC
authors.lastname: Yong
authors.forename: Chooi Hoong
authors.initials: CH
authors.lastname: Choo
authors.forename: Boon Hian
authors.initials: BH
authors.lastname: Tan
authors.forename: Chian-Ming
authors.initials: CM
authors.lastname: Low
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Bian
mesh_terms: D001923:Brain Chemistry / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D011494:Protein Kinases; D002118:Calcium; D006862:Hydrogen Sulfide