Effect of Sertraline on Ca^(2+) Fluxes in Rabbit Corneal Epithelial Cells

10.4077/CJP.2015.BAC255

Jeng-Hsien Yeh；Te-Kung Sun；Chiang-Ting Chou；Wei-Chuan Chen；Jenn-Kuen Lee；Hsiao-Chun Yeh；Wei-Zhe Liang；Chun-Chi Kuo；Pochuen Shieh；Daih-Huang Kuo；Chung-Ren Jan

Ca^(2+) ； corneal ； sertraline ； SIRC

The Chinese Journal of Physiology

58卷2期（2015 / 04 / 30）

85 - 94

英文

The effect of sertraline, a selective serotonin reuptake inhibitor (SSRI), on cytosolic free Ca^(2+) concentrations ([Ca^(2+)]_i) in a rabbit corneal epithelial cell line (SIRC) is unclear. This study explored whether sertraline changed basal [Ca^(2+)]_i levels in suspended SIRC cells by using fura-2 as a Ca^(2+)-sensitive fluorescent dye. Sertraline at concentrations between 10-100 μM increased [Ca^(2+)]_i in a concentrationdependent manner. The Ca^(2+) signal was reduced by 23% by removing extracellular Ca^(2+). Sertraline induced Mn^(2+) influx, leading to quench of fura-2 fluorescence, suggesting Ca^(2+) influx. This Ca^(2+) influx was inhibited by phospholipase A_2 inhibitor aristolochic acid, but not by store-operated Ca^(2+) channel blockers and protein kinase C/A modulators. In Ca^(2+)-free medium, pretreatment with the endoplasmic reticulum Ca^(2+) pump inhibitor thapsigargin, cyclopiazonic acid or 2,5-di-tert-butylhydroquinone greatly inhibited sertraline-induced Ca^(2+) release. Inhibition of phospholipase C with U73122 abolished sertralineinduced [Ca^(2+)]_i rise. At concentrations of 5-50 μM, sertraline killed cells in a concentration-dependent manner. The cytotoxic effect of 25 μM sertraline was not reversed by prechelating cytosolic Ca^(2+) with BAPTA/AM. Collectively, in SIRC cells, sertraline induced [Ca^(2+)]_i rises by causing phospholipase Cdependent Ca^(2+) release from the endoplasmic reticulum and Ca^(2+) influx via phospholipase A2-sensitive Ca^(2+) channels. Sertraline-caused cytotoxicity was mediated by Ca^(2+)-independent pathways.

1. Fang, Y.C.,Chou, C.T.,Pan, C.C.,Hsieh, Y.D.,Liang, W.Z.,Chao, D.,Tsai, J.Y.,Liao, W.C.,Kuo, D.H.,Shieh, P.,Kuo, C.C.,Jan, C.R.,Shaw, C.F.(2011).Paroxetine-induced Ca2+ movement and death in OC2 human oral cancer cells.Chinese J. Physiol.,54,310-317.
   連結：
2. Aldana, B.I.,Sitges, M.(2012).Sertraline inhibits pre-synaptic Na+ channel-mediated responses in hippocampus-isolated nerve endings.J. Neurochem.,121,197-205.
3. Alosaimi, F.D.,Baker, B.(2012).Clinical review of treatment options for major depressive disorder in patients with coronary heart disease.Saudi Med,33,1159-1168.
4. Amit, B.H.,Gil-Ad, I.,Taler, M.,Bar, M.,Zolokov, A.,Weizman, A.(2009).Proapoptotic and chemosensitizing effects of selective serotonin reuptake inhibitors on T cell lymphoma/leukemia (Jurkat) in vitro.Eur. Neuropsychopharmacol.,19,726-734.
5. Barbosa, F.B.,Capito, K.,Kofod, H.,Thams, P.(2002).Pancreatic islet insulin secretion and metabolism in adult rats malnourished during neonatal life.Brit. J. Nutr.,87,147-155.
6. Bazan, H.E.,Tao, Y.,DeCoster, M.A.,Bazan, N.G.(1997).Platelet-activating factor induces cyclooxygenase-2 gene expression in corneal epithelium: requirement of calcium in the signal transduction pathway.Invest. Ophthalmol. Vis. Sci.,38,2492-2501.
7. Becker, B.,Morel, N.,Vanbellinghen, A.M.,Lebrun, P.(2004).Blockade of calcium entry in smooth muscle cells by the antidepressant imipramine.Nature,68,833-842.
8. Clapham, D.E.(1995).Intracellular calcium. Replenishing the stores.Nature,375,634-635.
9. Deng, H.W.,Kwan, C.Y.(1991).Cyclopiazonic acid is a sarcoplasmic reticulum Ca2+-pump inhibitor of rat aortic muscle.Acta Pharmacol. Sin.,12,53-58.
10. Distelhorst, C.W.,Dubyak, G.(1998).Role of calcium in glucocorticosteroid-induced apoptosis of thymocytes and lymphoma cells: resurrection of old theories by new findings.Blood,91,731-734.
11. Florenzano, F.,Viscomi, M.T.,Cavaliere, F.,Volonté, C.,Molinari, M.(2006).The role of ionotropic purinergic receptors (P2X) in mediating plasticity responses in the central nervous system.Adv. Exp. Med. Biol.,557,77-100.
12. Gil-Ad, I.,Zolokov, A.,Lomnitski, L.,Taler, M.,Bar, M.,Luria, D.,Ram, E.,Weizman, A.(2008).Evaluation of the potential anticancer activity of the antidepressant sertraline in human colon cancer cell lines and in colorectal cancer-xenografted mice.Int. J. Oncol.,33,277-286.
13. Goodkin, M.L.,Epstein, S.,Asbell, P.A.,Blaho, J.A.(2007).Nuclear translocation of NF-κB precedes apoptotic poly(ADP-ribose) polymerase cleavage during productive HSV-1 replication in corneal epithelial cells.Invest. Ophthalmol. Vis. Sci.,48,4980-4988.
14. Harper, J.L.,Camerini-Otero, C.S.,Li, A.H.,Kim, S.A.,Jacobson, K.A.,Daly, J.W.(2003).Dihydropyridines as inhibitors of capacitativecalcium entry in leukemic HL-60 cells.Biochem. Pharmacol.,65,329-338.
15. Helmeste, D.M.,Tang, S.W.,Reist, C.,Vu, R.(1995).Serotonin uptake inhibitors modulate intracellular Ca2+ mobilization in platelets.Eur. J. Pharmacol.,288,373-377.
16. Hodge, J.M.,Wang, Y.,Berk, M.,Collier, F.M.,Fernandes, T.J.,Constable, M.J.,Pasco, J.A.,Dodd, S.,Nicholson, G.C.,Kennedy, R.L.,Williams, L.J.(2013).Selective serotonin reuptake inhibitors inhibit human osteoclast and osteoblast formation and function.Biol. Psychiatry,74,32-39.
17. Huang, J.K.,Chang, H.T.,Chou, C.T.,Shu, S.S.,Kuo, C.C.,Tsai, J.Y.,Liao, W.C.,Wang, J.L.,Lin, K.L.,Lu, Y.C.,Chen, I.S.,Liu, S.I.,Ho, C.M.,Jan, CR.(2011).The mechanism of sertraline-induced [Ca2+]i rise in human PC3 prostate cancer cells.Basic Clin. Pharmacol. Toxicol.,109,103-110.
18. Isaac, R.,Boura-Halfon, S.,Gurevitch, D.,Shainskaya, A.,Levkovitz, Y.,Zick, Y.(2013).Selective serotonin reuptake inhibitors (SSRIs) inhibit insulin secretion and action in pancreatic β cells.J. Biol. Chem.,288,5682-5693.
19. Kallenberg, L.A.(2000).Calcium signalling in secretory cells.Arch. Physiol. Biochem.,108,385-390.
20. Kalyoncu, N.I.,Ozyavuz, R.,Karaoglu, S.(1999).Sertraline inhibits the contractile responses to noradrenaline, KCl and electrical field stimulation of rat isolated vas deferens.J. Auton. Pharmacol.,19,365-369.
21. Kraus, D.,Kaiserman, I.,Frucht-Pery, J.,Rahamimoff, R.(2001).Calcium-an "all-round player" in the cornea.Isr. Med. Assoc. J.,3,269-274.
22. Kubo-Watanabe, S.,Satoh, Y.,Saino, T.(2002).Adenosine-5'- triphosphate-induced intracellular calcium changes through gapjunctional communication in the corneal epithelium.Jpn. J. Ophthalmol.,46,479-487.
23. Lee, H.A.,Kim, K.S.,Hyun, S.A.,Park, S.G.,Kim, S.J.(2012).Wide spectrum of inhibitory effects of sertraline on cardiac ion channels.Korean J. Physiol. Pharmacol.,16,327-332.
24. Li, Y.,Couch, L.,Higuchi, M.,Fang, J.L.,Guo, L.(2012).Mitochondrial dysfunction induced by sertraline, an antidepressant agent.Toxicol. Sci.,127,582-591.
25. Lin, K.L.,Chi, C.C.,Lu, T.,Tseng, L.L.,Wang, J.L.,Lu, Y.C.,Jan, C.R.(2013).Effect of sertraline on [Ca2+]i and viability of human MG63 osteosarcoma cells.Drug Chem. Toxicol.,36,231-240.
26. Lin, M.C.,Huang, C.C.,Huang, C.J.,Cheng, H.H.,Chou, C.T.,Wang, J.L.,Chen, I.S.,Liu, S.I.,Lu, Y.C.,Chang, H.T.,Huang, J.K.,Chen, J.S.,Jan, C.R.(2007).Ketoconazole-evoked [Ca2+]i rises and non-Ca2+-triggered cell death in rabbit corneal epithelial cells (SIRC).J. Recept. Signal. Transduct. Res.,27,295-307.
27. Liu, S.I.,Lin, K.L.,Lu, T.,Lu, Y.C.,Hsu, S.S.,Tsai, J.Y.,Liao, W.C.,Huang, F.D.,Chi, C.C.,Liang, W.Z.,Tseng, L.L.,Chiang, A.J.,Jan, C.R.(2013).M-3M3FBS-induced Ca² movement and apoptosis in HA59T human hepatoma cells.Chinese J. Physiol.,56,26-35.
28. Mauri, M.C.,Laini, V.,Cerveri, G.,Scalvini, M.E.,Volonteri, L.S.,Regispani, F.,Malvini, L.,Manfré, S.,Boscati, L.,Panza, G.(2002).Clinical outcome and tolerability of sertraline in major depression: a study with plasma levels.Prog. Neuropsychopharmacol. Biol. Psychiatry,26,597-601.
29. Muallem, S.,Loessberg, P.,Sachs, G.,Wheeler, L.A.(1991).Agonistsensitive and -insensitive intracellular Ca2+ pools. Separate Ca2+- releasing mechanisms revealed by manoalide and benzohydroquinone.Biochem. J.,279,367-375.
30. Putney, J.W. Jr.(1986).A model for receptor-regulated calcium entry.Cell Calcium,7,1-12.
31. Quinn, T.,Molloy, M.,Smyth, A.,Baird, A.W.(2004).Capacitative calcium entry in guinea pig gallbladder smooth muscle in vitro.Life Sci.,74,1659-1669.
32. Reddy, K.K.,Lefkove, B.,Chen, L.B.,Govindarajan, B.,Carracedo, A.,Velasco, G.,Carrillo, C.O.,Bhandarkar, S.S.,Owens, M.J.,Mechta-Grigoriou, F.,Arbiser, J.L.(2008).The antidepressant sertraline downregulates Akt and has activity against melanoma cells.Pigment. Cell Melanoma Res.,21,451-456.
33. Spanová, A.,Kovárů, H.,Lisá, V.,Lukásová, E.,Rittich, B.(1997).Estimation of apoptosis in C6 glioma cells treated with antidepressants.Physiol. Res.,46,161-164.
34. Taler, M.,Miron, O.,Gil-Ad, I.,Weizman, A.(2013).Neuroprotective and procognitive effects of sertraline: in vitro and in vivo studies.Neurosci. Lett.,550,93-97.
35. Thastrup, O.,Cullen, P.J.,Drøbak, B.K.,Hanley, M.R.,Dawson, A.P.(1990).Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+- ATPase.Proc. Natl. Acad. Sci. USA,87,2466-2470.
36. Thompson, A.K.,Mostafapour, S.P.,Denlinger, L.C.,Bleasdale, J.E.,Fisher, S.K.(1991).The aminosteroid U-73122 inhibits muscarinic receptor sequestration and phosphoinositide hydrolysis in SK-N-SH neuroblastoma cells. A role for Gp in receptor compartmentation.J. Biol. Chem.,266,23856-23862.
37. Tsien, R.Y.(1980).New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures.Biochemistry,19,2396-2404.
38. Wang, X.,Simpkins, J.W.,Dykens, J.A.,Cammarata, P.R.(2003).Oxidative damage to human lens epithelial cells in culture: estrogen protection of mitochondrial potential, ATP, and cell viability.Invest. Ophthalmol. Vis. Sci.,44,2067-2075.
39. Yagami, T.,Yamamoto, Y.,Kohma, H.,Nakamura, T.,Takasu, N.,Okamura, N.(2013).L-type voltage-dependent calcium channel is involved in the snake venom group IA secretory phospholipase A2-induced neuronal apoptosis.Neurotoxicology,35,146-153.
40. Young, R.C.,Schumann, R.,Zhang, P.(2001).Nifedipine block of capacitative calcium entry in cultured human uterine smoothmuscle cells.J. Soc. Gynecol. Investig.,8,210-215.
41. Zhang, F.,Wen, Q.,Mergler, S.,Yang, H.,Wang, Z.,Bildin, V.N.,Reinach, P.S.(2006).PKC isoform-specific enhancement of capacitative calcium entry in human corneal epithelial cells.Invest. Ophthalmol. Vis. Sci.,47,3989-4000.
42. Zhang, F.,Yang, H.,Wang, Z.,Mergler, S.,Liu, H.,Kawakita, T.,Tachado, S.D.,Pan, Z.,Capó-Aponte, J.E.,Pleyer, U.,Koziel, H.,Kao, W.W.,Reinach, P.S.(2007).Transient receptor potential vanilloid 1 activation induces inflammatory cytokine release in corneal epithelium through MAPK signaling.J. Cell. Physiol.,213,730-739.