Amitriptyline modulated Ca2+signaling and induced Ca2+-independent cell viability in human osteosarcoma cells
| Autor: | Wang Jl, Wei-Zhe Liang, Chiang-Ting Chou, I-Li Chen, Lu T, Kuo Cc, Chung-Ren Jan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Thapsigargin Phospholipase C Health Toxicology and Mutagenesis Endoplasmic reticulum General Medicine Pharmacology Toxicology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Phorbol medicine Amitriptyline Viability assay 030217 neurology & neurosurgery Protein kinase C medicine.drug Calcium signaling |
| Zdroj: | Human & Experimental Toxicology. 37:125-134 |
| ISSN: | 1477-0903 0960-3271 |
| DOI: | 10.1177/0960327117693070 |
| Popis: | Amitriptyline is a widely used tricyclic antidepressant, which acts primarily as a serotonin–norepinephrine reuptake inhibitor. This study examined the effect of amitriptyline on Ca2+homeostasis and its related mechanism in MG63 human osteosarcoma cells. Amitriptyline evoked cytosolic-free Ca2+concentrations ([Ca2+]i) rises concentration dependently. Amitriptyline-evoked Ca2+entry was confirmed by Mn2+-induced quench of fura-2 fluorescence. This entry was inhibited by Ca2+entry modulators nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate but was not affected by the PKC inhibitor GF109203X. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+pump inhibitor thapsigargin (TG) inhibited amitriptyline-evoked [Ca2+]irises by 95%. Conversely, treatment with amitriptyline abolished TG-evoked [Ca2+]irises. Inhibition of phospholipase C (PLC) with U73122 inhibited amitriptyline-evoked [Ca2+]irises by 70%. Amitriptyline killed cells at 200–500 μM in a concentration-dependent fashion. Chelating cytosolic Ca2+with 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid/AM did not reverse amitriptyline-induced cytotoxicity. Collectively, our data suggest that in MG63 cells, amitriptyline induced [Ca2+]irises by evoking PLC-dependent Ca2+release from the endoplasmic reticulum and Ca2+entry via PKC-regulated store-operated Ca2+entry. Amitriptyline also induced Ca2+-disassociated cell death. |
| Databáze: | OpenAIRE |
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