Chen Chung-Yi, Chen Ching-Hsein, Kung Chiu-Hu, Kuo Shih-Hsing, Kuo Soong-Yu
School of Medicine and Health Sciences, Department of Medical Technology, Fooyin University, Kaohsiung County, Taiwan, Republic of China.
J Nat Prod. 2008 Jan;71(1):137-40. doi: 10.1021/np070279y. Epub 2008 Jan 9.
[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.
[6]-姜辣素是从生姜（姜科植物姜）中提取的一种主要酚类化合物，是一种潜在的化学预防化合物，可在癌细胞中诱导应激并导致凋亡性细胞死亡。本研究考察了[6]-姜辣素对肾细胞的早期信号传导作用。研究发现，[6]-姜辣素以浓度依赖性方式引起细胞内钙离子浓度（[Ca2+]i）缓慢而持续的升高。去除细胞外钙离子时，[6]-姜辣素仍能诱导[Ca2+]i升高，但幅度降低了80%。用线粒体解偶联剂羰基氰化物间氯苯腙（CCCP）耗尽细胞内钙离子储存，并不影响[6]-姜辣素的作用。在无钙培养基中，用毒胡萝卜素（一种内质网钙离子泵抑制剂）耗尽储存的钙离子，可部分消除[6]-姜辣素诱导的[Ca2+]i升高。在含钙培养基中，蛋白激酶C活性的调节不影响[6]-姜辣素引起的[Ca2+]i升高。尼卡地平可阻断[6]-姜辣素诱导的钙离子内流。磷脂酶C抑制剂U73122可消除ATP（而非[6]-姜辣素）诱导的[Ca2+]i升高。这些发现表明，[6]-姜辣素通过尚未明确的机制刺激细胞外钙离子内流和毒胡萝卜素敏感的细胞内钙离子释放，从而诱导MDCK肾小管细胞中[Ca2+]i显著升高。
