[6]-gingerol induces Ca2+ mobilization in Madin-Darby canine kidney cells.
[6]-gingerol, a major phenolic compound derived from ginger (Zingiber officinale), is a potential chemopreventive compound that can induce stress in cancer cells and cause apoptotic cell death. This study examines the early signaling effects of [6]-gingerol on renal cells. It was found that [6]-gingerol caused a slow and sustained rise of [Ca2+]i in a concentration-dependent manner. [6]-gingerol also induced a [Ca2+]i rise when extracellular Ca2+ was removed, but the magnitude was reduced by 80%. Depletion of intracellular Ca2+ stores with CCCP, a mitochondrial uncoupler, did not affect the action of [6]-gingerol. In a Ca2+-free medium, the [6]-gingerol-induced [Ca2+]i rise was partially abolished by depleting stored Ca2+ with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). The elevation of [6]-gingerol-caused [Ca2+]i in a Ca2+-containing medium was not affected by modulation of protein kinase C activity. The [6]-gingerol-induced Ca2+ influx was blocked by nicardipine. U73122, an inhibitor of phospholipase C, abolished ATP (but not [6]-gingerol)-induced [Ca2+]i rise. These findings suggest that [6]-gingerol induces a significant rise in [Ca2+]i in MDCK renal tubular cells by stimulating both extracellular Ca2+ influx and thapsigargin-sensitive intracellular Ca2+ release via as yet unidentified mechanisms.
Chen
Chung-Yi
CY
School of Medicine and Health Sciences, Department of Medical Technology, Fooyin University, Kaohsiung County, Taiwan, Republic of China.
Chen
Ching-Hsein
CH
Kung
Chiu-Hu
CH
Kuo
Shih-Hsing
SH
Kuo
Soong-Yu
SY
D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002396:Catechols; D004285:Dogs; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D020939:Zingiber officinale / Q000737:chemistry*; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D015394:Molecular Structure; D009529:Nicardipine / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D013624:Taiwan; D019284:Thapsigargin / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D002396:Catechols; D005233:Fatty Alcohols; D019284:Thapsigargin; C007845:gingerol; D009529:Nicardipine