Ca2+ Signaling and Cell Death Induced by Protriptyline in HepG2 Human Hepatoma Cells

被引:1
|
作者
Wang, Jue-Long [1 ]
Chou, Chiang-Ting [2 ,3 ]
Liu, Kang [4 ]
Liang, Wei-Zhe [5 ]
Cheng, Jin-Shiung [6 ]
Chang, Hong-Tai [7 ]
Chen, I-Shu [7 ]
Lu, Ti [8 ]
Kuo, Chun-Chi [9 ]
Yu, Chia-Cheng [7 ]
Shieh, Pochuen [10 ]
Kuo, Daih-Huang [10 ]
Chen, Fu-An [10 ]
Jan, Chung-Ren [5 ]
机构
[1] Kaohsiung Vet Gen Hosp, Dept Rehabil, Tainan Branch, Tainan, Taiwan
[2] Chang Gung Inst Technol, Div Basic Med Sci, Dept Nursing, Chiayi, Taiwan
[3] Chang Gung Inst Technol, Chron Dis & Hlth Promot Res Ctr, Chiayi, Taiwan
[4] Kaohsiung Vet Gen Hosp, Dept Anesthesia, Tainan Branch, Tainan, Taiwan
[5] Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, Taiwan
[6] Kaohsiung Vet Gen Hosp, Dept Med, Kaohsiung, Taiwan
[7] Kaohsiung Vet Gen Hosp, Dept Surg, Kaohsiung, Taiwan
[8] Kaohsiung Vet Gen Hosp, Dept Psychiat, Kaohsiung 813, Taiwan
[9] Tzu Hui Inst Technol, Dept Nursing, Pingtung, Taiwan
[10] Tajen Univ, Dept Pharm, Pingtung, Taiwan
关键词
Ca2+; Cytotoxicity; Human Hepatoma Cells; Phospholipase C; Protriptyline; PROSTATE-CANCER CELLS; OBSTRUCTIVE PULMONARY-DISEASE; PROTEIN-COUPLED RECEPTORS; CALCIUM-ENTRY; TRICYCLIC ANTIDEPRESSANTS; ENDOPLASMIC-RETICULUM; NEUROBLASTOMA-CELLS; PLASMA-LEVELS; IN-VITRO; APOPTOSIS;
D O I
10.1002/jbt.21820
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effect of protriptyline on Ca2+ physiology in human hepatoma is unclear. This study explored the effect of protriptyline on [Ca2+](i) and cytotoxicity in HepG2 human hepatoma cells. Protriptyline (50-150M) evoked [Ca2+](i) rises. The Ca2+ entry was inhibited by removal of Ca2+. Protriptyline-induced Ca2+ entry was confirmed by Mn2+-induced quench of fura-2 fluorescence. Except nifedipine, econazole, SKF96365, GF109203X, and phorbol 12-myristate 13 acetate did not inhibit Ca2+ entry. Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) inhibited 40% of protriptyline-induced response. Treatment with protriptyline abolished BHQ-induced response. Inhibition of phospholipase C (PLC) suppressed protriptyline-evoked response by 70%. At 20-40M, protriptyline killed cells which was not reversed by the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in HepG2 cells, protriptyline induced [Ca2+](i) rises that involved Ca2+ entry through nifedipine-sensitive Ca2+ channels and PLC-dependent Ca2+ release from endoplasmic reticulum. Protriptyline induced Ca2+-independent cell death.
引用
收藏
页码:539 / 547
页数:9
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