Dataset Information

Effects of chlorogenic acid on intracellular calcium regulation in lysophosphatidylcholine-treated endothelial cells.

ABSTRACT: Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein (ox-LDL) and is implicated in its atherogenic activity. This study investigated the effects of LPC on cell viability, intracellular calcium homeostasis, and the protective mechanisms of chlorogenic acid (CGA) in human umbilical vein endothelial cells (HUVECs). LPC increased intracellular calcium ([Ca^2?]_i) by releasing Ca^2? from intracellular stores and via Ca^2? influx through store-operated channels (SOCs). LPC also increased the generation of reactive oxygen species (ROS) and decreased cell viability. The mRNA expression of Transient receptor potential canonical (TRPC) channel 1 was increased significantly by LPC treatment and suppressed by CGA. CGA inhibited LPC-induced Ca^2? influx and ROS generation, and restored cell viability. These results suggested that CGA inhibits SOC-mediated Ca^2? influx and ROS generation by attenuating TRPC1 expression in LPC-treated HUVECs. Therefore, CGA might protect endothelial cells against LPC injury, thereby inhibiting atherosclerosis. [BMB Reports 2017; 50(6): 323-328].

SUBMITTER: Jung HJ

PROVIDER: S-EPMC5498143 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of chlorogenic acid on intracellular calcium regulation in lysophosphatidylcholine-treated endothelial cells.

Jung Hye-Jin HJ Im Seung-Soon SS Song Dae-Kyu DK Bae Jae-Hoon JH

BMB reports 20170601 6

Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein (ox-LDL) and is implicated in its atherogenic activity. This study investigated the effects of LPC on cell viability, intracellular calcium homeostasis, and the protective mechanisms of chlorogenic acid (CGA) in human umbilical vein endothelial cells (HUVECs). LPC increased intracellular calcium ([Ca2＋]i) by releasing Ca2＋ from intracellular stores and via Ca2 ...[more]

PMID: 28088946

Similar Datasets

Project description:The cardiovascular effects of estrogen are mediated in part by augmenting the function of endothelial nitric oxide synthase. Endothelial nitric oxide synthase activity is dependent on many cofactors including Ca(2+). Hence, we investigated the effect of chronic 17 beta-estradiol treatment on the intracellular Ca(2+) concentration and endothelial nitric oxide synthase protein expression in the human endothelial cell line, EA.hy926, using spectrofluorometry and Western blot, respectively. Inhibiting the sarco(endo)plasmic reticulum Ca(2+) ATPase with thapsigargin caused an increase in the intracellular Ca(2+) concentration, which was higher in chronically 17 beta-estradiol-treated (1muM, 24h) cells loaded with Fura-2-acetoxymethyl ester compared to vehicle-treated cells, suggesting a higher endoplasmic reticulum Ca(2+) content in 17 beta-estradiol-treated cells. An enhanced Ca(2+) influx pathway in chronically 17 beta-estradiol-treated cells was also observed. In addition, 17 beta-estradiol-treated cells expressed higher levels of endothelial nitric oxide synthase protein in comparison to vehicle-treated cells. The chronic effect of 17 beta-estradiol on Ca(2+) homeostasis and endothelial nitric oxide synthase expression was attenuated with the nonselective estrogen receptor inhibitor, ICI 182,780 (10muM, 7alpha, 17beta-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl] estra-1,3,5(10)-triene-3,17-diol). Furthermore, analysis of the thapsigargin-evoked Ca(2+) response in chronically 17 beta-estradiol-treated estrogen receptor alpha-knockdown cells showed no significant difference in Ca(2+) response compared to vehicle-treated estrogen receptor alpha-knockdown cells, indicating that the regulation of Ca(2+) homeostasis by 17 beta-estradiol is mediated through an estrogen receptor alpha-dependent pathway. These data revealed an estrogen receptor alpha-dependent modulation of Ca(2+) homeostasis accompanying the enhancement of endothelial nitric oxide synthase expression in 17 beta-estradiol-treated human endothelial cells.

Project description:Major obstacles in current breast cancer treatment efficacy include the ability of breast cancer cells to develop resistance to chemotherapeutic drugs and the off-target cytotoxicity of these drugs on normal cells, leading to debilitating side effects. One major difference between cancer and normal cells is their metabolism, as cancer cells acquire glycolytic and mitochondrial metabolism alterations throughout tumorigenesis. In this study, we sought to exploit this metabolic difference by investigating alternative breast cancer treatment options based on the application of phytochemicals. Herein, we investigated three phytochemicals, namely cinnamaldehyde (CA), chlorogenic acid (CGA), and arctigenin (Arc), regarding their anti-breast-cancer properties. These phytochemicals were administered alone or in combination to MCF-7, MDA-MB-231, and HCC1419 breast cancer or normal MCF-10A and MCF-12F breast cells. Overall, our results indicated that the combination treatments showed stronger inhibitory effects on breast cancer cells versus single treatments. However, only treatments with CA (35 μM), CGA (250 μg/mL), and the combination of CA + CGA (35 μM + 250 μg/mL) showed no significant cytotoxic effects on normal mammary epithelial cells, suggesting that Arc was the driver of normal cell cytotoxicity in all other treatments. CA + CGA and, to a lesser extent, CGA alone effectively induced breast cancer cell death accompanied by decreases in mitochondrial membrane potential, increased mitochondrial superoxide, reduced mitochondrial and glycolytic ATP production, and led to significant changes in cellular and mitochondrial morphology. Altogether, the combination of CA + CGA was determined as the best anti-breast-cancer treatment strategy due to its strong anti-breast-cancer effects without strong adverse effects on normal mammary epithelial cells. This study provides evidence that targeting the mitochondria may be an effective anticancer treatment, and that using phytochemicals or combinations thereof offers new approaches in treating breast cancer that significantly reduce off-target effects on normal cells.

Dataset Information

Effects of chlorogenic acid on intracellular calcium regulation in lysophosphatidylcholine-treated endothelial cells.

Publications

Effects of chlorogenic acid on intracellular calcium regulation in lysophosphatidylcholine-treated endothelial cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets