title: Effect of allyl sulfides from garlic essential oil on intracellular ca2+ levels in renal tubular cells.
abstract: Diallyl sulfide (1), diallyl disulfide (2), and diallyl trisulfide (3), which are major organosulfur compounds of garlic (Allium sativum), are recognized as a group of potential chemopreventive compounds. In this study, the early signaling effects of 3 were examined on Madin-Darby canine kidney (MDCK) cells loaded with the Ca(2+)-sensitive dye fura-2. It was found that 3 caused an immediate and sustained increase of [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 40 μM). Compound 3 also induced a [Ca(2+)](i) elevation when extracellular Ca(2+) was removed, but the magnitude was reduced by 45%. In Ca(2+)-free medium, the 3-induced [Ca(2+)](i) level was abolished by depleting stored Ca(2+) with 1 μM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). Elevation of [Ca(2+)](i) caused by 3 in the Ca(2+)-containing medium was not affected by modulation of protein kinase C activity. The 3-induced Ca(2+) influx was inhibited by nifedipine and nicardipine (1 μM). U73122, an inhibitor of phospholipase C, abolished ATP (but not the 3-induced [Ca(2+)](i) level). These findings suggest that 3 induced a significant [Ca(2+)](i) elevation in MDCK renal tubular cells by stimulating both extracellular Ca(2+) influx and thapsigargin-sensitive intracellular Ca(2+) release via as yet unidentified mechanisms. Furthermore, the order of the allyl sulfide-induced [Ca(2+)](i) elevation and cell viability was 1 < 2 < 3. The differential effect of allyl sulfides on Ca(2+) signaling and cell death appears to correlate with the number of sulfur atoms in the structure of these allyl sulfides.
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
authors.forename: Horng-Ren
authors.initials: HR
authors.lastname: Lo
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Soong-Yu
authors.initials: SY
authors.lastname: Kuo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000498:Allyl Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000032:analysis* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D005737:Garlic / Q000737:chemistry*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D015394:Molecular Structure; D009529:Nicardipine / Q000494:pharmacology; D009822:Oils, Volatile / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D000498:Allyl Compounds; D004220:Disulfides; D009822:Oils, Volatile; D013440:Sulfides; C028009:diallyl disulfide; C038491:allyl sulfide; D000255:Adenosine Triphosphate; D009529:Nicardipine; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium