The garlic ingredient diallyl sulfide induces Ca(2+) mobilization in Madin-Darby canine kidney cells.
Diallyl sulfide (DAS), one of the major organosulfur compounds (OSCs) of garlic, is recognized as a group of potential chemoproventive compounds. In this study, we examines the early signaling effects of DAS on renal cells loaded with Ca(2+)-sensitive dye fura-2. It was found that DAS caused an immediate and sustained rise of [Ca(2+)](i) in a concentration-dependent manner (EC(50)=2.32 mM). DAS also induced a [Ca(2+)](i) elevation when extracellular Ca(2+) was removed, but the magnitude was reduced by 45%. Depletion of intracellular Ca(2+) stores with CCCP, a mitochondrial uncoupler, did not affect DAS's effect. In Ca(2+)-free medium, the DAS-induced [Ca(2+)](i) rise was abolished by depleting stored Ca(2+) with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). DAS-caused [Ca(2+)](i) rise in Ca(2+)-containing medium was not affected by modulation of protein kinase C activity. The DAS-induced Ca(2+) influx was blocked by nicardipine. U73122, an inhibitor of phospholipase C, abolished ATP (but not DAS)-induced [Ca(2+)](i) rise. Additionally, pretreatment with DAS for 24 h decreased cell viability in a concentration-dependent manner. Furthermore, DAS-induced cell death involved apoptotic events. These findings suggest that diallyl sulfide induced a significant rise in [Ca(2+)](i) in MDCK renal tubular cells by stimulating both extracellular Ca(2+) influx and thapsigargin-sensitive intracellular Ca(2+) release via as yet unidentified mechanisms.
Chen
Ching-Hsein
CH
Graduate Institute of Biomedical and Biopharmaceutical Sciences, College of Life Sciences, National Chiayi University, Chiayi, Taiwan.
Su
Shu-Jem
SJ
Chang
Kee-Lung
KL
Huang
Mei-Wen
MW
Kuo
Soong-Yu
SY
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D005737:Garlic / Q000737:chemistry*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009529:Nicardipine / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
D000498:Allyl Compounds; D000975:Antioxidants; D002121:Calcium Channel Blockers; D004963:Estrenes; D005456:Fluorescent Dyes; D010936:Plant Extracts; D011760:Pyrrolidinones; D013440:Sulfides; D014475:Uncoupling Agents; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C038491:allyl sulfide; D019284:Thapsigargin; D009529:Nicardipine; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2