Codonopsis lanceolata Contributes to Ca2+ Homeostasis by Mediating SOCE and PLC/IP3 Pathways in Vascular Endothelial and Smooth Muscle Cells

Abstract

Codonopsis lanceolata has been widely used as an anti-inflammatory and anti-lipogenic agent in traditional medicine. Recently, C. lanceolata was reported to prevent hypertension by improving vascular function. This study evaluated the effects of C. lanceolata and its major component lancemaside A on cytosolic calcium concentration in vascular endothelial cells and vascular smooth muscle cells. Cytosolic calcium concentration was measured using fura-2 AM fluorescence. C. lanceolata or lancemaside A increased the cytosolic calcium concentration by releasing Ca2+ from the endoplasmic reticulum and sarcoplasmic reticulum and by Ca2+ entry into endothelial cells and vascular smooth muscle cells from extracellular sources. The C. lanceolata- and lancemaside A-induced cytosolic calcium concentration increases were significantly inhibited by lanthanum, an inhibitor of non-selective cation channels, in both endothelial cells and vascular smooth muscle cells. Moreover, C. lanceolata and lancemaside A significantly inhibited store-operated Ca2+ entry under pathological extracellular Ca2+ levels. In Ca2+-free extracellular fluid, increases in the cytosolic calcium concentration induced by C. lanceolata or lancemaside A were significantly inhibited by U73122, an inhibitor of phospholipase C, and 2-APB, an inositol 1,4,5-trisphosphate receptor antagonist. In addition, dantrolene treatment, which inhibits Ca2+ release through ryanodine receptor channels, also inhibited C. lanceolata- or lancemaside A-induced increases in the cytosolic calcium concentration through the phospholipase C/inositol 1,4,5-trisphosphate pathway. These results suggest that C. lanceolata and lancemaside A increase the cytosolic calcium concentration through the non-selective cation channels and phospholipase C/inositol 1,4,5-trisphosphate pathways under physiological conditions and inhibit store-operated Ca2+ entry under pathological conditions in endothelial cells and vascular smooth muscle cells. C. lanceolata or lancemaside A can protect endothelial cells and vascular smooth muscle cells by maintaining cytosolic calcium concentration homeostasis, suggesting possible applications for these materials in diets for preventing vascular damage.

Ginsenoside Rg-1 prevents elevated cytosolic Ca2+ via store-operated Ca2+ entry in high-glucose–stimulated vascular endothelial and smooth muscle cells

“…EA and MOVAS cells were exposed to high glucose with or without Rg-1 for 48 hours. Cytosolic Ca 2+ was then measured using Fura-2 AM, a membrane-permeable, fluorescent ratiometric Ca 2+ -binding dye [ 20 ]. Approximately 1 × 10 6 /ml cells were incubated with 2.5 μM Fura-2 AM in the dark for 30 minutes at room temperature.…”

Cadmium exposure induces autophagy via PLC‐IP3‐IP3R signaling pathway in duck renal tubular epithelial cells

“…ER is the primary site of intracellular Ca preservation and Ca signal conductance. IP 3 R channel shoulders the principal mission of Ca 2+ release channel on ER membrane 16,28 . In Cd‐treated duck renal tubular epithelial cells of this research, the increase of [Ca 2+ ] c was accompanied by the increase of [Ca 2+ ] mit and the decrease of [Ca 2+ ] ER .…”

“…IP 3 R channel shoulders the principal mission of Ca 2+ release channel on ER membrane. 16,28 In Cdtreated duck renal tubular epithelial cells of this research, the increase enhanced the expression levels of the above genes and proteins. [30][31][32] In addition, the outcome also proved that the expression levels of these genes and proteins were markedly upregulated after Cd exposure, which provides further that Cd can cause an imbalance in Ca homeostasis.…”

Codonopsis lanceolata Extract Restores Smooth Muscle Vasorelaxation in Rat Carotid Arteries Even under High Extracellular K+ Concentrations

“…In a previous study, the oral administration of an ECL (200 or 400 mg/kg) in a rat model of hypertension rats had less of an effect compared with the administration of the L-type Ca 2+ channel blocker nifedipine, but it nonetheless significantly reduced systolic blood pressure compared with rats in a vehicle control group [19]. Moreover, lancemaside A, a major saponin component of an ECL, contributed to Ca 2+ homeostasis by inhibiting Ca 2+ influx through store-operated Ca 2+ entry in vascular smooth muscle cells [21], which suggests that effects of the ECL in this study could be induced by lancemaside A. Increased [K + ] o is a crucial factor that can cause changes in vascular tone [26].…”

“…Based on the previous studies, it is likely that that Ca 2+ channels are involved in the working mechanism of CL, similar to the case of nifedipine, a well-known Ca 2+ channel blocker that functions by inhibiting intracellular Ca 2+ influx into the blood vessels and heart. For example, an ECL contributed to Ca 2+ homeostasis in vascular endothelial and smooth muscle cells [21]. Also, an ECL showed a significant hypotensive effect in a hypertensive rat model, although not to the same degree as nifedipine [19].…”