Calcium signals and caspase-12 participated in paraoxon-induced apoptosis in EL4 cells.
In order to investigate whether calcium signals participate in paraoxon (POX)-induced apoptosis in EL4 cells, real-time laser scanning confocal microscopy (LSCM) was used to detect Ca(2+) changes during the POX application. Apoptotic rates of EL4 cells and caspase-12 expression were also evaluated. POX (1-10nM) increased intracellular calcium concentration ([Ca(2+)]i) in EL4 cells in a dose-dependent manner at early stage (0-2h) of POX application, and apoptotic rates of EL4 cells after treatment with POX for 16h were also increased in a dose-dependent manner. Pre-treatment with EGTA, heparin or procaine attenuated POX-induced [Ca(2+)]i elevation and apoptosis. Additionally, POX up-regulated caspase-12 expression in a dose-dependent manner, and pre-treatment with EGTA, heparin or procaine significantly inhibited POX-induced increase of caspase-12 expression. Our results suggested that POX induced [Ca(2+)]i elevation in EL4 cells at the early stage of POX-induced apoptosis, which might involve Ca(2+) efflux from the endoplasmic reticulum (ER) and Ca(2+) influx from extracellular medium. Calcium signals and caspase-12 were important upstream messengers in POX-induced apoptosis in EL4 cells. The ER-associated pathway possibly operated in this apoptosis.
Li
Lan
L
School of Life Sciences, Lanzhou University, Lanzhou 730000, PR China.
Cao
Zhiheng
Z
Jia
Pengfei
P
Wang
Ziren
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects*; D053454:Caspase 12 / Q000096:biosynthesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D010261:Paraoxon / Q000633:toxicity*; D011343:Procaine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects
D015220:Calcium Channels; D002614:Chelating Agents; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007306:Insecticides; D019837:Ryanodine Receptor Calcium Release Channel; D011343:Procaine; D004533:Egtazic Acid; D006493:Heparin; D053454:Caspase 12; D010261:Paraoxon; D002118:Calcium