PMID- 23613483 OWN - NLM STAT- MEDLINE DCOM- 20131111 LR - 20171116 IS - 1477-0903 (Electronic) IS - 0960-3271 (Linking) VI - 32 IP - 4 DP - 2013 Apr TI - Effect of diindolylmethane on Ca(2+) homeostasis and viability in MDCK renal tubular cells. PG - 344-53 LID - 10.1177/0960327112462727 [doi] AB - The effect of the natural product diindolylmethane (DIM) on cytosolic Ca(2+) concentrations ([Ca(2+)]i) and viability in MDCK renal tubular cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)]i. DIM at concentrations 1-50 muM induced a [Ca(2+)]i rise in a concentration-dependent manner. The response was reduced partly by removing Ca(2+). DIM induced Mn(2+) influx leading to quenching of fura-2 fluorescence. DIM-evoked Ca(2+) entry was suppressed by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In the absence of extracellular Ca(2+), incubation with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ) greatly inhibited DIM-induced [Ca(2+)]i rise. Incubation with DIM abolished TG or BHQ-induced [Ca(2+)]i rise. Inhibition of phospholipase C with U73122 reduced DIM-induced [Ca(2+)]i rise by 50%. At 1, 10, 40 and 50 muM, DIM slightly enhanced cell proliferation. The effect of 50 muM DIM was reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. In sum, in MDCK cells, DIM induced a [Ca(2+)]i rise by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via protein kinase C-sensitive store-operated Ca(2+) channels. DIM did not induce cell death. FAU - Fang, Y-C AU - Fang YC AD - Department of Laboratory Medicine, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan. FAU - Chou, C-T AU - Chou CT FAU - Chi, C-C AU - Chi CC FAU - Lin, K-L AU - Lin KL FAU - Li, Y-D AU - Li YD FAU - Cheng, H-H AU - Cheng HH FAU - Lu, Y-C AU - Lu YC FAU - Cheng, J-S AU - Cheng JS FAU - Kuo, C-C AU - Kuo CC FAU - Jan, C-R AU - Jan CR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Hum Exp Toxicol JT - Human & experimental toxicology JID - 9004560 RN - 0 (Biological Products) RN - 0 (Indoles) RN - EC 3.1.4.- (Type C Phospholipases) RN - SSZ9HQT61Z (3,3'-diindolylmethane) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Biological Products/*pharmacology MH - Calcium/*metabolism MH - Cell Survival/drug effects MH - Dogs MH - Endoplasmic Reticulum/drug effects/metabolism MH - Homeostasis/drug effects MH - Indoles/*pharmacology MH - Kidney Tubules/cytology MH - Madin Darby Canine Kidney Cells MH - Type C Phospholipases/metabolism EDAT- 2013/04/25 06:00 MHDA- 2013/11/12 06:00 CRDT- 2013/04/25 06:00 PHST- 2013/04/25 06:00 [entrez] PHST- 2013/04/25 06:00 [pubmed] PHST- 2013/11/12 06:00 [medline] AID - 0960327112462727 [pii] AID - 10.1177/0960327112462727 [doi] PST - ppublish SO - Hum Exp Toxicol. 2013 Apr;32(4):344-53. doi: 10.1177/0960327112462727.