Effect of hydrogen sulfide on intracellular calcium homeostasis in neuronal cells.
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.
Yong
Qian Chen
QC
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore.
Choo
Chooi Hoong
CH
Tan
Boon Hian
BH
Low
Chian-Ming
CM
Bian
Jin-Song
JS
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
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D011494:Protein Kinases; D002118:Calcium; D006862:Hydrogen Sulfide