Effect of diindolylmethane on Ca(2+) homeostasis and viability in MDCK renal tubular cells
| Autor: | Chung-Ren Jan, Lu Yc, Yi-Chien Fang, Chiang-Ting Chou, Kuo Cc, Li Yd, Cheng Js, Chi Cc, Lin Kl, He-Hsiung Cheng |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Thapsigargin
Indoles Cell Survival Health Toxicology and Mutagenesis Diindolylmethane Biology Toxicology Endoplasmic Reticulum Madin Darby Canine Kidney Cells chemistry.chemical_compound Dogs Extracellular Animals Homeostasis Protein kinase C Biological Products Phospholipase C Cell growth Endoplasmic reticulum General Medicine Cell biology Cytosol Kidney Tubules chemistry Type C Phospholipases Biophysics Calcium |
| Zdroj: | Humanexperimental toxicology. 32(4) |
| ISSN: | 1477-0903 |
| Popis: | The effect of the natural product diindolylmethane (DIM) on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in MDCK renal tubular cells was explored. The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i. DIM at concentrations 1–50 μM induced a [Ca2+]i rise in a concentration-dependent manner. The response was reduced partly by removing Ca2+. DIM induced Mn2+ influx leading to quenching of fura-2 fluorescence. DIM-evoked Ca2+ entry was suppressed by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In the absence of extracellular Ca2+, incubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ) greatly inhibited DIM-induced [Ca2+]i rise. Incubation with DIM abolished TG or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 reduced DIM-induced [Ca2+]i rise by 50%. At 1, 10, 40 and 50 μM, DIM slightly enhanced cell proliferation. The effect of 50 μM DIM was reversed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane- N, N, N', N'-tetraacetic acid. In sum, in MDCK cells, DIM induced a [Ca2+]i rise by evoking phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via protein kinase C-sensitive store-operated Ca2+ channels. DIM did not induce cell death. |
| Databáze: | OpenAIRE |
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