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研究生:方譯謙
研究生(外文):Yi-chien Fang
論文名稱:藥物m-3m3FBS與paroxetine對人類口腔癌細胞與狗腎臟細胞內鈣離子平衡及誘發細胞死亡機制之探討
論文名稱(外文):The effect of m-3m3FBS and paroxetine on calcium homeostasis and viability in OC2 human oral cancer cells and canine MDCK renal tubular cells
指導教授:簡崇仁簡崇仁引用關係蕭正夫
指導教授(外文):Chung-Ren JanChen-Fu Shaw
學位類別:博士
校院名稱:國立中山大學
系所名稱:生物科學系研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:英文
論文頁數:147
中文關鍵詞:BAPTAm-3M3FBS腎臟MDCK細胞口腔癌OC2細胞鈣離子細胞凋亡細胞壞疽tBHPH2O2caspaseparoxetine
外文關鍵詞:NecrosistBHPH2O2caspaseparoxetineApoptosisOC2 cellsMDCK cellsm-3M3FBSCa2+BAPTA
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m-3M3FBS能夠刺激細胞內鈣離子濃度的上升,且細胞內鈣離子濃度的上升是經由PLC (Phosphoinositide-specific phospholipase C)的活化路徑來完成,由於PLC常常參與在各種不同細胞的細胞訊息傳遞反應過程中,因此這種刺激作用是否一樣適用於腎臟MDCK細胞以及口腔癌OC2細胞,仍未可知。所以我們將利用鈣離子敏感的螢光染料fura-2來探討m-3M3FBS對於腎臟MDCK細胞以及口腔癌OC2細胞活化PLC的分子機轉,以及PLC調節的細胞訊息傳遞的相關作用。我們發現0.1-20 μM m-3M3FBS會造成MDCK細胞內鈣離子濃度的上昇,而且細胞內鈣離子濃度會隨著藥物濃度的升高而上昇,然而在OC2細胞,m-3M3FBS的濃度須達到10-60 μM才會造成細胞內鈣離子濃度的上昇;當移除細胞外鈣離子,會稍微降低m-3M3FBS造成的細胞內鈣離子濃度上昇,表示細胞內鈣離子濃度的上昇有一部分是因為細胞外鈣離子的流入,而這種細胞外鈣離子的流入會受到鈣離子通道抑制劑nifedipine、econazole、SK&F96365以及phospholipase A2抑制劑aristolochic acid的影響。於無鈣溶液中,經由m-3M3FBS前處理的細胞,會完全抑制內質網鈣離子幫浦抑制劑(例如thapsigargin、cyclopiazonic acid 或者2,5-di-tert-butylhydroquinone (BHQ))引起之細胞內鈣離子上升,相反的,利用thapsigargin、cyclopiazonic acid 或者BHQ前處理的細胞,會部份抑制m-3M3FBS作用所引起之細胞內鈣離子上升,而且m-3M3FBS造成的細胞內鈣離子的釋放不會因為PLC的抑制劑U73122的作用而改變。總之,研究結果顯示,m-3M3FBS誘發MDCK和OC2細胞內鈣離子濃度的增加,是經由與PLC無關的內質網鈣離子通道釋放而來,以及store-operated鈣離子通道的流入,還有尚未確定發現的鈣離子通道所共同影響。除了鈣離子濃度的變化,我們發現m-3M3FBS濃度介於5至100 μM 時,其毒殺OC2細胞的能力與濃度呈正比,且細胞內鈣離子敖合劑1,2-bis(2-aminophenoxy)ethane- N,N,N'',N''-tetraacetic acid (BAPTA) 並不會抑制m-3M3FBS的細胞毒殺效用。Propidium iodide螢光染色的流體細胞實驗測定發現20 μM及50 μM的m-3M3FBS會誘發與鈣離子無關的細胞凋亡。
由實驗的結果知道m-3M3FBS會誘發與鈣離子無關的細胞凋亡,但是這與其他人發表的研究結果有所不同,因此我們也有興趣得知細胞內鈣離子敖合劑BAPTA是否也能抑制氧化壓力造成的MDCK細胞的死亡,以及這樣的死亡過程是否與m-3M3FBS誘發與鈣離子無關的細胞凋亡相同。我們發現BAPTA能夠抑制tBHP和H2O2誘發的細胞死亡,而且BAPTA的濃度愈高抑制細胞死亡的效果愈好,因此我們推測tBHP和H2O2誘發的MDCK細胞死亡是與鈣離子相關的細胞死亡。接著我們利用2 μM U73122 (PLC抑制劑)、50 μM zVAD-fmk (caspase抑制劑)、2 μM cyclosporin A (MPTP抑制劑)、20 μM PD98059 (ERK抑制劑)、2 μM SP600125 (JNK抑制劑)…等,都沒有發現能夠抑制tBHP和H2O2誘發的MDCK細胞死亡,推測tBHP和H2O2誘發的MDCK細胞死亡並不是經由PLC, MPTP, caspase, ERK或者JNK的路徑。從propidium iodide螢光染色、caspase-3活性分析以及倒立顯微鏡下的細胞形態的結果讓我們認為tBHP和H2O2誘發的MDCK細胞死亡並不是走細胞凋亡的路徑,它比較像是細胞壞疽,而且是caspase無關、鈣離子相關的細胞死亡。
抗憂鬱藥物paroxetine對於人類口腔癌細胞OC2細胞內鈣離子細胞訊息傳遞的作用仍未可知,因此我們也利用鈣離子敏感的螢光染料fura-2來探討paroxetine對於口腔癌OC2細胞內調節鈣離子濃度的相關作用。我們發現100-1000 μM paroxetine會造成OC2細胞內鈣離子濃度的上昇,而且細胞內鈣離子濃度會隨著藥物濃度的升高而上昇;當移除細胞外鈣離子,會降低50%左右的paroxetine造成的細胞內鈣離子濃度上昇,表示細胞內鈣離子濃度的上昇有50%是因為細胞外鈣離子的流入,而這種細胞外鈣離子的流入會受到鈣離子通道抑制劑nifedipine、econazole、SK&F96365、phospholipase A2抑制劑aristolochic acid以及蛋白質激酶C的影響而被抑制。於無鈣溶液中,經由內質網鈣離子幫浦抑制劑thapsigargin前處理的細胞,會完全抑制paroxetine造成OC2細胞內鈣離子濃度上昇的作用,而且paroxetine造成的細胞內鈣離子的釋放不會因為PLC的抑制劑U73122的作用而改變。除了鈣離子濃度的變化,我們發現paroxetine濃度介於10至50 μM 時,其毒殺OC2細胞的能力與濃度呈正比,且細胞內鈣離子敖合劑BAPTA並不會抑制paroxetine的細胞毒殺效用。Propidium iodide螢光染色的流體細胞實驗測定發現paroxetine會誘發與鈣離子無關的細胞凋亡。總之,研究結果顯示,paroxetine誘發OC2細胞內鈣離子濃度的增加,是經由與PLC無關的內質網鈣離子通道釋放而來,以及phospholipase A2和蛋白質激酶C有關的store-operated鈣離子通道的流入,至於paroxetine造成的細胞死亡是與鈣離子無關的細胞凋亡作用。
The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)- benzenesulfonamide (m-3M3FBS), a presumed phospholipase C activator, on cytosolic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells and OC2 human oral cancer cells was unclear. This study explored whether m-3M3FBS changed basal [Ca2+]i levels in suspended MDCK and OC2 cells by using fura-2 as a Ca2+-sensitive fluorescent dye. m-3M3FBS at concentrations between 0.1-20 μM increased [Ca2+]i in a concentration-dependent manner in MDCK cells, however in OC2 cells, m-3M3FBS at concentrations between 10-60 μM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signals were reduced partly by removing extracellular Ca2+ in the two cell types. m-3M3FBS-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers nifedipine, econazole and SK&F96365, and by the phospholipase A2 inhibitor aristolochic acid. In Ca2+-free medium, m-3M3FBS pretreatment abolished the [Ca2+]i rise induced by the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin, cyclopiazonic acid or 2,5-di-tert-butylhydroquinone (BHQ). Conversely, pretreatment with thapsigargin, cyclopiazonic acid or BHQ partly reduced m-3M3FBS-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter m-3M3FBS-induced [Ca2+]i rise. Collectively, in MDCK and OC2 cells, m-3M3FBS induced [Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via store-operated Ca2+ channels and other unidentified Ca2+ channels. Additionally, 5-100 μM of m-3M3FBS killed cells in a concentration-dependent manner in OC2 cells. The cytotoxic effect of m-3M3FBS was not reversed by prechelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane- N,N,N'',N''-tetraacetic acid (BAPTA). Propidium iodide staining data suggest that m-3M3FBS (20 or 50 μM) induced apoptosis in a Ca2+-independent manner.
We were also interested in knowing whether BAPTA suppressed cell death during oxidative stress in MDCK cells. BAPTA loading altered tBHP (tert-butyl hydroperoxide) and H2O2-induced cell death in a concentration-dependent manner. This suggests that the cell death induced by tBHP and H2O2 appears to be Ca2+-dependent in MDCK cells. The tBHP and H2O2-induced cell death was not suppressed by 2 μM U73122 (PLC inhibitor), 50 μM zVAD-fmk (caspase inhibitor), 2 μM cyclosporin A (a potent inhibitor of the MPTP), 20 μM PD98059 (ERK inhibitor) or 2 μM SP600125 (JNK inhibitor). This suggests that the tBHP and H2O2-induced MDCK cells death was not via the PLC, MPTP, caspase, ERK or JNK pathways. Propidium iodide staining, caspase-3 activity assay and cell morphology data suggest that tBHP and H2O2-induced cell death was necrosis, not via apoptosis, and the cell death appears to be caspase-independent and Ca2+-dependent.
The effect of the antidepressant paroxetine on [Ca2+]i in OC2 human oral cancer cells is unclear. This study also explored whether paroxetine changed basal [Ca2+]i levels in suspended OC2 cells by using fura-2 as a Ca2+-sensitive fluorescent dye. Paroxetine at concentrations between 100-1000 μM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 50% by removing extracellular Ca2+. Paroxetine-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers nifedipine, econazole and SK&F96365, the phospholipase A2 inhibitor aristolochic acid, and protein kinase C modulators. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished paroxetine–induced [Ca2+]i rise. Inhibition of PLC with U73122 did not alter paroxetine-induced [Ca2+]i rise. Paroxetine at 10-50 μM induced cell death in a concentration-dependent manner. The death was not reversed when cytosolic Ca2+ was chelated with BAPTA. Propidium iodide staining suggests that apoptosis played a role in the death. Collectively, in OC2 cells, paroxetine induced [Ca2+]i rise by causing PLC-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via store-operated Ca2+ channels in a manner regulated by protein kinase C and phospholipase A2. Paroxetine also induced cell death in a Ca2+-independent manner.
學位論文審定書………………………..……………… i
誌謝…………………………………………………...... ii
中文摘要……………………………………………….. iii
Abstract………………………………………………… v
Contents…………………………………………........ viii
List of figures…………………………………………… x
List of abbreviations…………………………………… xii
Chapter 1: Introduction………………………………… 1
Apoptosis…………………………………………… 1
Calcium homeostasis…………………………….. 6
Mitogen-activated protein kinases (MAPKs).…… 9
m-3M3FBS………………………………………..... 13
Reactive oxygen species (ROS)………………… 16
Paroxetine………………………………………… ..20
Specific aims...…………………………………….. 22
Chapter 2: Effect of m-3M3FBS on Ca2+ movement in MDCK and OC2 cells.……………………………….. 25
2.1 Introduction…………………………………… 25
2.2 Materials and methods…………………....... 27
2.3 Results………………………………………… 32
2.4 Discussion…………………………………….. 43
Chapter 3: Paroxetine-induced Ca2+ Movement and Death in OC2 Human Oral Cancer Cells………….. 54
3.1 Introduction…………………………………… 54
3.2 Materials and methods…………………….. 56
3.3 Results………………………………………… 60
3.4 Discussion………………………………….. 63
Chapter 4: Conclusions……………………............ 68
References…………………………………………… 72
Figures……………………………………………… 84
Publications and Presentations……………........ 116
Appendix 1: Effect of m-3M3FBS on Ca2+ movement in Madin-Darby canine renal tubular cells. Hum Exp Toxicol 2009; 28: 655-663. …..…………… 118
Appendix 2: Paroxetine-induced Ca2+ Movement and Death in OC2 Human Oral Cancer Cells. Chin J Physiol 2011; 54. In press.………………….......... 127
Albert, A.P., Large, W.A. Activation of store-operated channels by noradrenaline via protein kinase C in rabbit portal vein myocytes. J Physiol 2002; 544: 113-125.
Amoroso, S., Gioielli, A., Cataldi, M., Renzo, G.D., Annunziato, L. In the neuronal cell line SH-SY5Y, oxidative stress-induced free radical overproduction causes cell death without any participation of intracellular Ca2+ increase. Biochim Biophys Acta 1999; 1452: 151-160.
Annunziato, L., Amoroso, S., Pannaccione, A., Cataldi, M., Pignataro, G., D''Alessio, A., Sirabella, R., Secondo, A., Sibaud, L., Di Renzo, G. F. Apoptosis induced in neuronal cells by oxidative stress: role played by caspases and intracellular calcium ions. Toxicol Lett 2003; 139: 125-133.
Aoki, H., Kang, P.M., Hampe, J., Yoshimura, K., Noma, T., Matsuzaki, M., Izumo, S. Direct Activation of Mitochondrial Apoptosis Machinery by c-Jun N-terminal Kinase in Adult Cardiac Myocytes. J Biol Chem 2002; 277: 10244-10250.
Bae, Y.S., Lee, T.G., Park, J.C., Hur, J.H., Kim, Y., Heo, K. Identification of a compound that directly stimulates phospholipase C activity. Mol Pharmacol 2003; 63: 1043-1050.
Baines, C.P., Kaiser1, R.A., Purcell1, N.H., Blair, N.S., Osinska1, H., Hambleton, M.A., Brunskill, E.W., Sayen, M.R., Gottlieb, R.A., Dorn II, G.W., Robbins, J., Molkentin, J.D. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 2005; 434: 658-662.
Berridge M.J. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 2002; 32: 235-249.
Berridge M.J., Bootman M.D., Roderick H.L. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 2003; 4: 517-529
Boittin, F.X., Gribi, F., Serir, K., Bény, J.L. Ca2+-independent PLA2 controls endothelial store-operated Ca2+ entry and vascular tone in intact aorta. Am J Physiol Heart Circ Physiol 2008; 295: H2466-H2474.
Boittin, F.X., Petermann, O., Hirn, C., Mittaud, P., Dorchies, O.M., Roulet, E, Ruegg, U.T. Ca2+-independent phospholipase A2 enhances store-operated Ca2+ entry in dystrophic skeletal muscle fibers. J Cell Sci 2006; 119: 3733-3742.

Bootman, M.D., Berridge, M.J., Roderick, H.L. Calcium signalling: more messengers, more channels, more complexity. Cur Biol 2002; 12: R563-R565.
Brenner, D., Mak, T.W. Mitochondrial cell death effectors. Curr Opin Cell Biol 2009, 21: 871-877
Chandra, J., Samamli, A., Orrenius, S. Triggering and modulation of apoptosis by oxidative stress. Free Radical Biol Med 2000; 29: 323-333.
Chauhan, D., Li, G., Hideshima, T., Podar, K., Mitsiades, C., Mitsiades, N., Munshi, N., Kharbanda, S., Anderson, K.C. JNK-dependent Release of Mitochondrial Protein, Smac, during Apoptosis in Multiple Myeloma (MM) Cells. J Biol Chem 2003; 278: 17593-17596.
Chen, W.C., Huang, C.C., Huang, C.J., Chien, J.M., Lin, K.L., Lu, Y.C., Chen, I.S., Liu, S.I., Hsu, S.S., Chang, H.T., Chou, C.T., Jan, C.R. Mechanism of paroxetine-induced cell death in renal tubular cells. Basic Clin Pharmacol Toxicol 2008; 103: 407-413.
Choi, S.E., Min, S.H., Shin, H.C., Kim, H.E., Jung, M.W., Kang, Y. Involvement of calcium-mediated apoptotic signals in H2O2-induced MIN6N8a cell death. Eur J Pharmacol 2006; 547: 1-9.
Chou, C.T., He, S., Jan, C.R. Paroxetine-induced apoptosis in human osteosarcoma cells: activation of p38 MAP kinase and caspase-3 pathways without involvement of [Ca2+]i elevation. Toxicol Appl Pharmacol 2007; 218: 265-273.
Chu, S.T., Huang, C.C., Huang, C.J., Cheng, J.S., Chai, K.L., Cheng, H.H., Fang, Y.C., Chi, C.C., Su, H.H., Chou, C.T., Jan, C.R. Tamoxifen-induced [Ca2+]i rises and Ca2+-independent cell death in human oral cancer cells. J Recept Signal Transduct Res 2007; 27: 353-367.
Clapham, D.E. Intracellular calcium. Replenishing the stores. Nature 1995; 375: 634-635.
Clapp, T.R., Medler, K.F., Damak, S., Margolskee, R.F., Kinnamon, S.C. Mouse taste cells with G protein-coupled taste receptors lack voltage-gated calcium channels and SNAP-25. BMC Biol 2006; 4: 7.
Craig, E.A., Stevens, M.V., Vaillancourt, R.R., Camenisch, T.D. MAP3Ks as central regulators of cell fate during development. Dev Dyn 2008; 237: 3102-3114.

Cregan, S.P., Dawson, V.L., Slack, R.S. Role of AIF in caspase-dependent and caspase- independent cell death. Oncogene 2004; 23: 2785-2796.
Crompton, M., Ellinger, H., Costi, A. Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress. Biochem J 1988; 255: 357-360.
Danial, N.N., Korsmeyer, S.J. Cell death: critical control points. Cell 2004, 116: 205-219.
Das, A., Banik, N.L., Ray, S.K. Garlic compounds generate reactive oxygen species leading to activation of stress kinases and cysteine proteases for apoptosis in human glioblastoma T98G and U87MG cells. Cancer 2007; 110: 1083-1095.
Das, S., Bhattacharyya, S., Ghosh, S., Majumdar, S. TNF-alpha induced altered signaling mechanism in human neutrophil. Mol Cell Biochem 1999; 197: 97-108.
Díaz Añel, A.M. Phospholipase C β3 is a key component in the Gβγ/PKCη/ PKD-mediated regulation of trans-Golgi network to plasma membrane transport. Biochem J 2007; 406: 157-165.
Dick, I.E., Brochu, R.M., Purohit, Y., Kaczorowski, G.J., Martin, W.J., Priest, B.T. Sodium channel blockade may contribute to the analgesic efficacy of antidepressants. J Pain 2007; 8: 315-324.
Dumaz, N., Marais, R. Integrating signals between cAMP and the RAS/RAF/MEK/ERK signalling pathways. Based on the anniversary prize of the Gesellschaft fur Biochemie und Molekularbiologie Lecture delivered on 5 July 2003 at the Special FEBS Meeting in Brussels. FEBS J 2005; 272: 3491-3504.
Dunn, K.L., Espino, P.S., Drobic, B., He, S., Davie, J.R. The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling. Biochem Cell Biol 2005; 83: 1-14.
Duvernay, M.T., Filipeanu, C.M., Wu, G. The regulatory mechanisms of export trafficking of G protein-coupled receptors. Cell Signal 2005; 17: 1457-1465.
Dwyer, L., Kim, H.J., Koh, B.H., Koh, S.D. Phospholipase C-independent effects of 3M3FBS in murine colon. Eur J Pharmacol 2010; 628: 187-194.
Florenzano, F., Viscomi, M.T., Mercaldo, V., Longone, P., Bernardi, G., Bagni, C. P2X2R purinergic receptor subunit mRNA and protein are expressed by all hypothalamic hypocretin/orexin neurons. J Com Neurol 2006; 498: 58-67.
Gil-Ad, I., Zolokov, A., Lomnitski, L., Taler, M., Bar, M., Luria, D., Ram, E., Weizman, A. Evaluation of the potential anti-cancer activity of the antidepressant sertraline in human colon cancer cell lines and in colorectal cancer-xenografted mice. Int J Oncol 2008; 33: 277-286.
Giorgio, M., Trinei, M., Migliaccio, E., Pelicci, P.G. Hydrogen peroxide: a metabolic by‑product or a common mediator of ageing signals? Nat Rev Mol Cell Biol 2007; 8: 722-728.
Goldstein, D.M., Gabriel, T. Pathway to the clinic: inhibition of P38 MAP kinase. A review of ten chemotypes selected for development. Curr Top Med Chem 2005; 5: 1017-1029.
Grynkiewicz, G., Poenie, M., Tsien, R.Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 1985; 260: 3440-3450.
Haidara, K., Morel, I., Abalea, V., Barre, M.G., Denizeau, F. Mechanism of tert-butyl- hydroperoxide induced apoptosis in rat hepatocytes: involvement of mitochondria and endoplasmic reticulum. Biochim Biophys Acta 2002; 1542: 173-185.
Halestrap, A. A pore way to die. Nature 2005; 434: 578-579.
Halliwell, B. Antioxidants in human health and disease. Annu Rev Nutr 1996; 16: 33-50.
Hamilton, S.L. Ryanodine receptors. Cell Calcium 2005; 38: 253-260.
Harper, J.L., Camerini-Otero, C.S., Li, A.H., Kim, S.A., Jacobson, K.A., Daly, J.W. Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells. Biochem Pharmacol 2003; 65: 329-338.
Hattori, T., Wang, P.L. Calcium antagonists cause dry mouth by inhibiting resting saliva secretion. Life Sci 2007; 81: 683-690.
Henry-Mowatt1, J., Dive1, C., Martinou, J.C., James, D. Role of mitochondrial membrane permeabilization in apoptosis and cancer. Oncogene 2004; 23: 2850-2860.
Hills, C.E., Brunskill, N.J. Intracellular signalling by C-peptide. Exp Diabetes Res 2008; 2008: 635158.
Horowitz, L.F., Hirdes, W., Suh, B.C., Hilgemann, D.W., Mackie, K., Hille, B. Phospholipase C in living cells: activation, inhibition, Ca2+ requirement, and regulation of M current. J Gen Physiol 2005; 126: 243-262.
Huang, C., Huang, C.J., Cheng, J., Liu, S.I, Tsai, J., Chou, C.T., Tseng, P., Jan, C.R. Fendiline-evoked [Ca2+]i rises and non-Ca2+-triggered cell death in human oral cancer cells. Hum Exp Toxicol 2009; 28: 41-48.
Huang, J.K., Huang, C.J., Chen, W.C., Liu, S.I., Hsu, S.S., Chang, H.T., Tseng, L.L., Chou, C.T., Chang, C.H., Jan, C.R. Independent [Ca2+]i increases and cell proliferation induced by the carcinogen safrole in human oral cancer cells. Naunyn Schmiedebergs Arch Pharmacol 2005; 372: 88-94.
Ishikawa, J., Ohga, K., Yoshino, T., Takezawa, R., Ichikawa, A., Kubota, H., Yamada, T. A pyrazole derivative, YM-58483, potently inhibits store-operated sustained Ca2+ influx and IL-2 production in T lymphocytes. J Immunol 2003; 170: 4441-4449.
Jajoo, S., Mukherjea, D., Brewer, G.J., Ramkumar, V. Pertussis toxin B-oligomer suppresses human immunodeficiency virus-1 Tat-induced neuronal apoptosis through feedback inhibition of phospholipase C-beta by protein kinase C. Neuroscience 2008; 151: 525-532.
Jan, C.R., Ho, C.M., Wu, S.N., Tseng, C.J. The phospholipase C inhibitor U73122 increases cytosolic calcium in MDCK cells by activating calcium influx and releasing stored calcium. Life Sci 1998; 63: 895-908.
Jan, C.R., Chou K.J., Lee, K.C., Wang, J.L., Tseng, L.L., Cheng, J.S., Chen, W.C. Dual action of palmitoyl trifluoromethyl ketone (PACOCF3) on Ca2+ signaling: activation of extracellular Ca2+ influx and alteration of ATP- and bradykinin-induced Ca2+ responses in Madin Darby canine kidney cells. Arch Toxicol 2000a; 74: 447-451.
Jan, C.R., Tseng, C.J. MK-886, a leukotriene biosynthesis inhibitor, as an activator of Ca2+ mobilization in Madin-Darby canine kidney (MDCK) cells. J Pharmacol Exp Ther 2000b; 294: 96-102.
Jiang, N., Zhang, Z.M., Liu, L., Zhang, C., Zhang, Y.L., Zhang, Z.C. Effects of Ca2+ channel blockers on store-operated Ca2+ channel currents of Kupffer cells after hepatic ischemia/reperfusion injury in rats. World J Gastroenterol 2006; 12: 4694-4698.
Jung, E.M., Lee, T.J., Park, J.W., Bae, Y.S., Kim, S.H., Choi, Y.H., Kwon T.K. The novel phospholipase C activator, m-3M3FBS, induces apoptosis in tumor cells through caspase activation, down-regulation of XIAP and intracellular calcium signaling. Apoptosis 2008; 13: 133-145.

Karin, M. Inflammation-activated protein kinases as targets for drug development. Proc Am Thorac Soc 2005; 2: 386-90; discussion 394-395.
Kerr, J.F., Wyllie, A.H., Currie, A.R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239-257.
Kim, J.A., Kang, Y.S., Kim, Y.O., Lee, S.H., Lee, Y.S. Role of Ca2+ influx in the tert- butyl hydroperoxide-induced apoptosis of HepG2 human hepatoblastoma cells. Exp Mol Med 1998; 30: 137-144.
Knorr, U., Kessing, L.V. The effect of selective serotonin reuptake inhibitors in healthy subjects. A systematic review. Nord J Psychiatry 2010; 64: 153-163.
Kobayashi, T., Washiyama, K., Ikeda, K. Inhibition of G protein-activated inwardly rectifying K+ channels by the antidepressant paroxetine. J Pharmacol Sci 2006; 102: 278-287.
Korchak, H.M., Corkey, B.E., Yaney, G.C., Kilpatrick, L.E. Negative regulation of ligand-initiated Ca2+ uptake by PKC-beta II in differentiated HL60 cells. Am J Physiol Cell Physiol 2001; 281: C514-C523.
Kowaltowskia, A.J., Castilhob, R.F., Vercesib, A.E. Mitochondrial permeability transition and oxidative stress. FEBS Letters 2001; 495: 12-15.
Krjukova, J., Holmqvist, T., Danis, A.S., Akerman, K.E., Kukkonen J.P. Phospholipase C activator m-3M3FBS affects Ca2+ homeostasis independently of phospholipase C activation. Br J Pharmacol 2004; 143: 3-7.
Kroemer, G. Mitochondrial control of apoptosis: an introduction. Biochem Biophys Res Commun 2003; 304: 433-435.
Kuo, L.N., Huang, C.J., Fang, Y.C., Huang, C.C., Wang, J.L., Lin, K.L., Chu, S.T., Chang, H.T., Chien, J.M., Su, H.H., Chi, C.C., Chen, W.C., Tsai, J.Y., Liao, W.C., Tseng, L.L., Jan, C.R. Effect of thimerosal on Ca2+ movement and viability in human oral cancer cells. Hum Exp Toxicol 2009; 28: 301-308.
Lang, F., Paulmichl, M. Properties and regulation of ion channels in MDCK cells. Kidney Int 1995; 48: 1200-1205.
Large, W.A., Saleh, S.N., Albert, A.P. Role of phosphoinositol 4,5-bisphosphate and diacylglycerol in regulating native TRPC channel proteins in vascular smooth muscle. Cell Calcium 2009; 45: 574-582.

Lee, Y.N., Lee, H.Y., Kim, J.S., Park, C., Choi, Y.H., Lee, T.G., Ryu, S.H., Kwak, J.Y., Bae Y.S. The novel phospholipase C activator, m-3M3FBS, induces monocytic leukemia cell apoptosis. Cancer Lett 2005; 222: 227-235.
Levkovitz, Y., Gil-Ad, I., Zeldich, E., Dayag, M., Weizman, A. Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines: evidence for p-c-Jun, cytochrome c, and caspase-3 involvement. J Mol Neurosci 2005; 27: 29-42.
Li, H.F., Shen, A.Y., Jan, C.R., Wu, S.N. Co-activation of nonselective cation channels by store depletion and oxidative stress in monocytic U937 cells. Chin J Physiol 1998; 41: 113-119.
Lin, C.H., Liu, M.C., Lin, M.S., Lin, P.L., Chen, Y.H., Chen, C.T., Chen, I.M., Tsai, M.C. Effects of a new isoquinolinone derivative on induction of action potential bursts in central snail neuron. Pharmacology 2005; 75: 98-110.
Lin, C.C., Yang, J.S., Chen, J.T., Fan, S., Yu, F.S., Yang, J.L., Lu, C.C., Kao, M.C., Huang, A.C., Lu, H.F., Chung, J.G. Berberine induces apoptosis in human HSC-3 oral cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway. Anticancer Res 2007; 27: 3371-3378.
Liu, S.I., Cheng, H.H., Huang, C.J., Chang, H.C., Chen, W.C., Chen, I.S., Hsu, S.S., Chang, H.T., Huang, J.K., Chen, J.S., Lu, Y.C., Jan, C.R. Melittin-induced [Ca2+]i increases and subsequent death in canine renal tubular cells. Hum Exp Toxicol 2008; 27: 417-424.
Liu, Z., Tao, X., Zhang, C., Lu, Y., Wei, D. Protective effects of hyperoside (quercetin-3-o-galactoside) to PC12 cells against cytotoxicity induced by hydrogen peroxide and tert-butyl hydroperoxide. Biomed Pharmacother 2005; 59: 481-490.
Lovborg, H., Gullbo, J., Larsson, R. Screening for apoptosis--classical and emerging techniques. Anticancer Drugs 2005; 16: 593-599.
Lu, C.H., Su, W., Lo, Y.K., Chen, W.C., Chang, W.N., Wang, J.L., Tsai, Y.C., Lee, P.Y., Jan, C.R. Effect of t-butyl hydroperoxide on Ca2+ movement in PC12 pheochromocytoma cells. Chin J Physiol 2002; 45: 51-56.
Lupescu, A., Bock, C.T., Lang, P.A., Aberle, S., Kaiser, H., Kandolf, R., Lang, F. Phospholipase A2 activity-dependent stimulation of Ca2+ entry by human parvovirus B19 capsid protein VP1. J Virol 2006; 80: 11370-11380.

Luttrell, L.M. Composition and function of G protein-coupled receptor signalsomes controlling mitogen-activated protein kinase activity. J Mol Neurosci 2005; 26: 253-264.
Ma, R., Pluznick, J., Kudlacek, P., Sansom, S.C. Protein kinase C activates store-operated Ca2+ channels in human glomerular mesangial cells. J Biol Chem 2001; 276: 25759-25765.
Marchant, J.S. Cellular signalling: STIMulating calcium entry. Curr Biol 2005; 15: R493-R495.
Martin, H., Flandez, M., Nombela, C., Molina, M. Protein phosphatases in MAPK signalling: we keep learning from yeast. Mol Microbiol 2005; 58: 6-16.
Masand, P.S., Gupta, S. Selective Serotonin-Reuptake Inhibitors: An Update. Harvard Review of Psychiatry 1999; 7: 69-84.
Matuszyk, J., Kobzdej, M., Ziolo, E., Kalas, W., Kisielow, P., Strzadala, L. Thymic lymphomas are resistant to Nur77-mediated apoptosis. Biochem Biophys Res Commu 1998; 249: 279-282.
McInnes, C., Fischer, P.M. Strategies for the design of potent and selective kinase inhibitors. Curr Pharm Des 2005; 11: 1845-1863.
Merritt, J.E., Jacob, R., Hallam, T.J. Use of manganese to discriminate between calcium influx and mobilization from internal stores in stimulated human neutrophils. J Biol Chem 1989; 264: 1522-1527.
Mohamad, N., Gutiérrez, A., Núñez, M., Cocca, C., Martín, G., Cricco, G., Medina, V., Rivera, E., Bergoc, R. Mitochondrial apoptotic pathways. Biocell 2005; 29: 149-161.
Morita, K., Sakakibara, A., Kitayama, S., Kumagai, K., Tanne, K., Dohi, T. Pituitary adenylate cyclase-activating polypeptide induces a sustained increase in intracellular free Ca2+ concentration and catechol amine release by activating Ca2+ influx via receptor-stimulated Ca2+ entry, independent of store-operated Ca2+ channels, and voltage-dependent Ca2+ channels in bovine adrenal medullary chromaffin cells. J Pharmacol Exp Ther 2002; 302: 972-982.
Nakagawa, T., Shimizu1, S., Watanabe, T., Yamaguchi, O., Otsu, K., Yamagata1, H., Inohara, H., Kubo, T., Tsujimoto1, Y. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 2005; 434: 652-658.
Nagata, K., Imai, T., Yamashita, T., Tsuda, M., Tozaki-Saitoh, H., Inoue, K. Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief. Mol Pain 2009; 5: 20.
Nam, J.H., Lee, H.S., Nguyen, Y.H., Kang, T.M., Lee, S.W., Kim, H.Y., Kim, S.J., Earm, Y.E., Kim, S.J. Mechanosensitive activation of K+ channel via phospholipase C-induced depletion of phosphatidylinositol 4,5-bisphosphate in B lymphocytes. J Physiol 2007; 582: 977-990.
Nicholson, D.W. Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ 1999; 6: 1028-1042.
Nishimura, K., Tsumagari, H., Setoyama, T., Morioka, A., Lu, S., Jisaka, M., Nagaya, T., Yokota, K. Prostaglandin F(2alpha) is protective for apoptosis stimulated synergistically with 12-O-tetradecanoyl phorbol-beta-acetate and nordihydroguaiaretic acid in Madin-Darby canine kidney cells. Biochim Biophys Acta 2004; 1682: 102-111.
Orrenius, S., Zhivotovsky, B., Nicotera, P. Regulation of the cell death: the calcium- apoptosis link. Nat Rev Mol Cell Biol 2003; 4: 552-565.
Orton, R.J., Sturm, O.E., Vyshemirsky, V., Calder, M., Gilbert, D.R., Kolch, W. Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway. Biochem J 2005; 392: 249-261.
Pan, C.C., Kuo, D.H., Shieh, P., Chen, F.A., Kuo, C.C., Jan, C.R. Effect of the antidepressant paroxetine on Ca2+ movement in PC3 human prostate cancer cells. Drug Development Research 2010; 71: 120-126.
Pinton, P., Giorgi, C., Siviero, R., Zecchini, E and Rizzuto, R. Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene 2008; 27: 6407-6418.
Piret, J.P., Arnould, T., Fuks, B., Chatelain, P., Remacle, J., Michiels, C. Mitochondria permeability transition-dependent tert-butyl hydroperoxide-induced apoptosis in hepatoma HepG2 cells. Biochemical Pharmacology 2004; 67: 611-620.
Putney JW Jr. A model for receptor-regulated calcium entry. Cell Calcium 1986; 7: 1-12.
Quinn, T., Molloy, M., Smyth, A., Baird, A.W. Capacitative calcium entry in guinea pig gallbladder smooth muscle in vitro. Life Sci 2004; 74: 1659-1669.

Racagni, G., Popoli, M. Cellular and molecular mechanisms in the long-term action of antidepressants. Dialog Clin Neurosci 2008; 10: 385-400.
Ramezani-Rad M. The role of adaptor protein Ste50-dependent regulation of the MAPKKK Ste11 in multiple signalling pathways of yeast. Curr Genet 2003; 43: 161-170.
Rao, J.N., Liu, L., Zou, T., Marasa, B.S., Boneva, D., Wang, S.R., Malone, D.L., Turner, D.J., Wang, J.Y. Polyamines are required for phospholipase C-gamma1 expression promoting intestinal epithelial restitution after wounding. Am J Physiol Gastrointest Liver Physiol 2007; 292: G335-G343.
Rosetti, M., Frasnelli, M., Tesei, A., Zoli, W., Conti, M. Cytotoxicity of different selective serotonin reuptake inhibitors (SSRIs) against cancer cells. J Exp Ther Oncol 2006; 6: 23-29.
Roy, S.S., Hajnoczky, G. Calcium, mitochondria and apoptosis studied by fluorescence measurements. Methods 2008; 46: 213-223.
Saleh, S.N., Albert, A.P., Peppiatt-Wildman, C.M., Large, W.A. Diverse properties of store-operated TRPC channels activated by protein kinase C in vascular myocytes. J Physiol 2008; 586: 2463-2476.
Santella, L., Ercolano, E., Nusco, G.A. The cell cycle: a new entry in the field of Ca2+ signaling. Cell Mol Life Sci 2005; 62:2405-2413.
Scholl, F.A., Dumesic, P.A., Khavari, P.A. Effects of active MEK1 expression in vivo. Cancer Lett 2005; 230: 1-5.
Schuster, C., Fernbach, N., Rix, U., Superti-Furga, G., Holy, M., Freissmuth, M., Sitte, H.H., Sexl, V. Selective serotonin reuptake inhibitors--a new modality for the treatment of lymphoma/leukaemia? Biochem Pharmacol 2007; 74: 1424-1435.
Shideman, C.R., Reinardy, J.L., Thayer, S.A. gamma-Secretase activity modulates store-operated Ca2+ entry into rat sensory neurons. Neurosci Lett 2009; 451: 124-128.
Singaravelu, K., Lohr, C., Deitmer, J.W. Calcium-independent phospholipase A2 mediates store-operated calcium entry in rat cerebellar granule cells. Cerebellum 2008; 7: 467-481.
Sohal, R.S. Oxidative stress hypothesis of aging. Free Radic Biol Med 2002; 33: 573-574.
Strasser, A. The role of BH3-only proteins in the immune system. Nat Rev Immunol 2005, 5: 189-200.
Sundaram, M.V. RTK/Ras/MAPK signaling. WormBook 2006; 11: 1-19.
Takahashi, T., Tanaka, M., Brannan, C.I., Jenkins, N.A., Copeland, N.G., Suda, T., Nagata, S. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 1994; 76: 969-976.
Tedesco, E., Rigoni, M., Caccin, P., Grishin, E., Rossetto, O., Montecucco, C. Calcium overload in nerve terminals of cultured neurons intoxicated by alpha-latrotoxin and snake PLA2 neurotoxins. Toxicon 2009; 54: 138-144.
Thastrup, O., Cullen, P.J., Drobak, B.K., Hanley, M.R., Dawson, A.P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Pro Natl Acad Sci USA 1990; 87: 2466-2470.
Thompson, A.K., Mostafapour, S.P., Denlinger, L.C., Bleasdale, J.E., Fisher, S.K. 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 1991; 266: 23856-23862.
Torii, S., Nakayama, K., Yamamoto, T., Nishida, E. Regulatory mechanisms and function of ERK MAP kinases. J Biochem (Tokyo). 2004; 136: 557-561.
Tsien, R.Y. New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. Biochemistry 1980; 19: 2396-2404.
Uhlik, M.T., Abell, A.N., Cuevas, B.D., Nakamura, K., Johnson, G.L. Wiring diagrams of MAPK regulation by MEKK1, 2, and 3. Biochem Cell Biol 2004; 82: 658-663.
Vallon, V. P2 receptors in the regulation of renal transport mechanisms. Am J Physiol Renal Physiol 2008; 294: F10-F27.
Wada, T., Penninger, J.M. Mitogen-activated protein kinase in apoptosis regulation. Oncogen 2004; 23: 2838-2849.
Wang, G.K., Mitchell, J., Wang, S.Y. Block of persistent late Na+ currents by antidepressant sertraline and paroxetine. J Membr Biol 2008; 222: 79-90.

Wang, J.L., Lin, K.L., Chen, W.C., Chou, C.T., Huang, C.J., Liu, C.S., Hsieh, C.H., Chang, C.H., Huang, J.K., Chang, H.T., Liu, S.I., Hsu, S.S., Jan, C.R. Effect of celecoxib on Ca2+ fluxes and proliferation in MDCK renal tubular cells. J Recept Signal Transduct Res 2005; 25: 237-249.
Wassenberg, J.J., Clark, K.D., Nelson, D.L. Effect of SERCA pump inhibitors on chemoresponses in Paramecium. J Eukaryot Microbiol 1997; 44: 574-581.
Watanabe-Fukunaga, R., Brannan, C.I., Copeland, N.G., Jenkins, N.A., Nagata, S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 1992; 356: 314-317.
Werry, T.D., Wilkinson, G.F., Willars, G.B. Mechanisms of cross-talk between G-protein-coupled receptors resulting in enhanced release of intracellular Ca2+. Biochem J 2003; 374: 281-296.
Wrobleski, S.T., Doweyko, A.M. Structural comparison of p38 inhibitor-protein complexes: a review of recent p38 inhibitors having unique binding interactions. Curr Top Med Chem 2005; 5:1005-1016.
Xia, Z., Dickens, M., Raingeaud, J., Davis, R.J., Greenberg, M.E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995; 270: 1326-1331.
Yeh, J.H., Cheng, H.H., Huang, C.J., Chung, H.M., Chiu, H.F., Yang, Y.L., Yeh, M.Y., Chen, W.C., Kao, C.H., Chou, C.T., Jan, C.R. Effect of anandamide on cytosolic Ca2+ levels and proliferation in canine renal tubular cells. Basic Clin Pharmacol Toxicol 2006; 98: 416-422.
Young, R.C., Schumann, R., Zhang, P. Nifedipine block of capacitative calcium entry in cultured human uterine smooth-muscle cells. J Soc Gynecol Investig 2001; 8: 210-215.
Zhang, B., Ma, J.X. SERPINA3K prevents oxidative stress induced necrotic cell death by inhibiting calcium overload. PLoS ONE 2008; 3: e4077.
Zong, W.X., Lindsten, T., Ross, A.J., MacGregor, G.R., Thompson, C.B. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev 2001, 15: 1481-1486.
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