Rb1 restores palmitic acid-induced reduction of Ca2+ influx by activating PLC in EA cells and PLD in MOVAS cells

Abstract

Recent interest has focused on the role of Ca²⁺ in regulating health problems, including cardiovascular disease and colorectal cancer. The inverse correlation between colon cancer and serum Ca²⁺ underlines the importance of understanding intracellular Ca²⁺ dynamics. Studies are also evaluating the contributions of abnormalities in Ca²⁺ homeostasis and intracellular dysfunction to the pathogenesis of metabolic syndrome as a precursor of cardiovascular disease. In this study, we investigated the changes of Ca²⁺ dynamics and ginsenoside Rb₁ (Rb₁)-induced recovery in two vascular cell lines exposed to palmitic acid (PA), the most abundant active ingredient in palm oil. The mechanism underlying the Rb₁-induced recovery was examined in a store operated Ca²⁺ entry model by Ca²⁺ store depletion. PA reduced the Ca²⁺ influx in both EA.hy926 (EA) and MOVAS cells, and this change was restored by Rb₁. In EA cells, the Rb₁-induced restoration was abolished by U73122 or 2-APB. In MOVAS cells, meanwhile, the effect of Rb₁ was abolished by FIPI, U73122 and U73343. Under normal conditions, Rb₁ itself altered phospholipid signaling (PLC in EA cells and PLD in MOVAS cells), but did not affect Ca²⁺ homeostasis. These differences resulted in differences in downstream actions, as KB-R7943 and nifedipine inhibited Rb₁-mediated Ca²⁺ influx recovery only in MOVAS cells. In conclusion, Rb₁ rescues the PA-induced Ca²⁺ influx by appropriately activating PLC in EA cells and PLD in MOVAS cells. This demonstrates that Ca²⁺ dynamics are elaborately regulated via intracellular Ca²⁺ signaling networks, suggesting a potential strategy for maintaining vascular Ca²⁺ homeostasis in hyperlipidemic environments.