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Title: Deltamethrin-Induced [Ca ²⁺ ]i Rise and Death in HGB Human Glioblastoma Cells. Author: Hsu SS, Chou CT. Journal: Chin J Physiol; 2012 Aug 31; 55(4):294-304. PubMed ID: 23282171. Abstract: The effect of the pesticide deltamethrin on cytosolic free Ca ²⁺ 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 5-60 μM increased [Ca²⁺]i in a concentration-dependent fashion. The Ca²⁺ signal was reduced partly by removing extracellular Ca ²⁺ . Deltamethrin induced Mn ²⁺ entry leading to quenching of fura-2 fluorescence. Deltamethrin-induced [Ca²⁺ ]i rise was not inhibited by nifedipine, econazole, SKF96365, 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, 50 μM 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 80 μM 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 (10-40 μM) 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.[Abstract] [Full Text] [Related] [New Search]