Deltamethrin-Induced [Ca2+]i Rise and Death in HGB Human Glioblastoma Cells

10.4077/CJP.2012.BAB114

Shu-Shong Hsu；Chiang-Ting Chou；Wei-Chuan Liao；Wei-Zhe Liang；Chun-Chi Kuo；Hsuan Chen；Yu-Ting Chen；Szu-Yuan Liu；Chung-Ren Jan

poptosis ； Ca2+ ； deltamethrin ； glioblastoma

The Chinese Journal of Physiology

55卷4期（2012 / 08 / 01）

294 - 304

英文

The effect of the pesticide deltamethrin on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in human glioblastoma DBTRG-05MG cells is explored. [Ca2+]i was measured in suspended cells using fura-2 as a Ca2+-sensitive fluorescent dye. Deltamethrin at concentrations of 5-60μM increased [Ca2+]i in a concentration-dependent fashion. The Ca2+ signal was reduced partly by removing extracellular Ca2+. Deltamethrin induced Mn2+ entry leading to quenching of fura-2 fluorescence. Deltamethrin-induced [Ca2+]i rise was not inhibited by nifedipine, econazole, SK&F96365, and phorbol 12-myristate 13 acetate, but was inhibited by the protein kinase C (PKC) inhibitor GF109203X via blocking Ca2+ release. In Ca2+-free medium, 50μM deltamethrin pretreatment abolished the [Ca2+]I rise induced by the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) or 2, 5-di-tertbutylhydroquinone (BHQ). Conversely, pretreatment with TG/BHQ abolished deltamethrin-induced [Ca2+]i rise. Inhibition of inositol 1, 4, 5-trisphosphate formation with U73122 suppressed 50% of deltamethrin-induced [Ca2+]i rise. At concentrations between 10 and 80μM deltamethrin killed cells in a concentration-dependent manner. The cytotoxic effect of deltamethrin was not reversed by prechelating cytosolic Ca2+ with 1, 2-bis (2-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid (BAPTA). Annexin V/ propidium iodide staining data suggest that deltamethrin (10-40μM) induced apoptosis in a concentrationdependent manner. Deltamethrin also increased levels of reactive oxygen species. Together, in human glioblastoma cells, deltamethrin induced a [Ca2+]i rise by inducing phospholipase C- and PKC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via non-store-operated Ca2+ channels. Deltamethrin induced cell death that might involve apoptosis via mitochondrial pathways.

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