Effect of toluene diisocyanate on homeostasis of intracellular-free calcium in human neuroblastoma SH-SY5Y cells.
The mechanisms of TDI (2,4-toluene diisocyanate)-induced occupational asthma are not fully established. Previous studies have indicated that TDI induces non-specific bronchial hyperreactivity to methacholine and induces contraction of smooth muscle tissue by activating 'capsaicin-sensitive' nerves resulting asthma. Cytosolic-free calcium ion concentrations ([Ca(2+)](c)) are elevated when either capsaicin acts at vanilloid receptors, or methacholine at muscarinic receptors. This study therefore investigated the effects of TDI on Ca(2+) mobilization in human neuroblastoma SH-SY5Y cells. TDI was found to elevate [Ca(2+)](c) by releasing Ca(2+) from the intracellular stores and extracellular Ca(2+) influx. 500 microM TDI induced a net [Ca(2+)](c) increase of 112+/-8 and 78+/-6 nM in the presence and absence of extracellular Ca(2+), respectively. In Ca(2+)-free buffer, TDI induced Ca(2+) release from internal stores to reduce their Ca(2+) content and this reduction was evidenced by a suppression occurring on the [Ca(2+)](c) rise induced by thapsigargin, ionomycin, and methacholine after TDI incubation. In the presence of extracellular Ca(2+), simultaneous exposure to TDI and methacholine led a higher level of [Ca(2+)](c) compared to single methacholine stimulation, that might explain that TDI induces bronchial hyperreactivity to methacholine. We conclude that TDI is capable of interfering the [Ca(2+)](c) homeostasis including releasing Ca(2+) from internal stores and inducing extracellular Ca(2+) influx. The interaction of this novel character and bronchial hyperreactivity need further investigation.
Liu
Pei-Shan
PS
Department of Microbiology, Soochow University, Shihlin, Taipei, Taiwan, R.O.C. psliu@mail.scu.edu.tw
Chiung
Yin-Mei
YM
Kao
Yi-Yun
YY
D001285:Atropine / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D018738:Hexamethonium / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014051:Toluene 2,4-Diisocyanate / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines; D043587:Receptor, Muscarinic M3; D016210:Methacholine Chloride; D014051:Toluene 2,4-Diisocyanate; D018738:Hexamethonium; D004533:Egtazic Acid; D015759:Ionomycin; D019284:Thapsigargin; D001285:Atropine; D014700:Verapamil; C082748:epibatidine; D011188:Potassium; D002118:Calcium