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Ca 2+ Signaling and Cell Death Induced by Protriptyline in HepG2 Human Hepatoma Cells
Author(s) -
Wang JueLong,
Chou ChiangTing,
Liu Kang,
Liang WeiZhe,
Cheng JinShiung,
Chang HongTai,
Chen IShu,
Lu Ti,
Kuo ChunChi,
Yu ChiaCheng,
Shieh Pochuen,
Kuo DaihHuang,
Chen FuAn,
Jan ChungRen
Publication year - 2016
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21820
Subject(s) - bapta , endoplasmic reticulum , chemistry , phospholipase c , nifedipine , intracellular , phorbol , phospholipase , pharmacology , biophysics , microbiology and biotechnology , calcium , biochemistry , protein kinase c , biology , signal transduction , enzyme , organic chemistry
ABSTRACT The effect of protriptyline on Ca 2+ physiology in human hepatoma is unclear. This study explored the effect of protriptyline on [Ca 2+ ] i and cytotoxicity in HepG2 human hepatoma cells. Protriptyline (50–150 μM) evoked [Ca 2+ ] i rises. The Ca 2+ entry was inhibited by removal of Ca 2+ . Protriptyline‐induced Ca 2+ entry was confirmed by Mn 2+ ‐induced quench of fura‐2 fluorescence. Except nifedipine, econazole, SKF96365, GF109203X, and phorbol 12‐myristate 13 acetate did not inhibit Ca 2+ entry. Treatment with the endoplasmic reticulum Ca 2+ 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 20–40 μM, protriptyline killed cells which was not reversed by the Ca 2+ chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid‐acetoxymethyl ester (BAPTA/AM). Together, in HepG2 cells, protriptyline induced [Ca 2+ ] i rises that involved Ca 2+ entry through nifedipine‐sensitive Ca 2+ channels and PLC‐dependent Ca 2+ release from endoplasmic reticulum. Protriptyline induced Ca 2+ ‐independent cell death.

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