TY - JOUR
T1 - Codonopsis lanceolata Contributes to Ca 2+Homeostasis by Mediating SOCE and PLC/IP 3Pathways in Vascular Endothelial and Smooth Muscle Cells
AU - Kim, Min Kyung
AU - Han, A. Young
AU - Shin, You Kyoung
AU - Lee, Kwang Won
AU - Seol, Geun Hee
N1 - Funding Information:
This work was supported by a grant from the National Research Foundation of Korea Forest Service (KFS-2016005C10-1719-AB01) and Basic Science Research Program through the National Research Foundation of Korea (NRF-2018R1D1A1B07050048). This manuscript is a revision of M.K.K.’s masterʼs thesis from Korea University.
Funding Information:
This work was supported by a grant from the National Research Foundation of Korea Forest Service (KFS-2016005C10-1719-AB01) and Basic Science Research Program through the National Research Foundation of Korea (NRF-2018R1D1A1B07050048). This manuscript is a revision of M.K.K.'s master's thesis from Korea University.
Publisher Copyright:
© 2021 American Society of Civil Engineers (ASCE). All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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 Ca 2+from the endoplasmic reticulum and sarcoplasmic reticulum and by Ca 2+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 Ca 2+entry under pathological extracellular Ca 2+levels. In Ca 2+-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 Ca 2+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 Ca 2+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.
AB - 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 Ca 2+from the endoplasmic reticulum and sarcoplasmic reticulum and by Ca 2+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 Ca 2+entry under pathological extracellular Ca 2+levels. In Ca 2+-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 Ca 2+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 Ca 2+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.
KW - Campanulaceae
KW - Codonopsis lanceolate
KW - inositol 1,4,5-trisphosphate
KW - store-operated Ca entry
KW - vascular endothelial cells
KW - vascular smooth muscle cells
UR - http://www.scopus.com/inward/record.url?scp=85092253500&partnerID=8YFLogxK
U2 - 10.1055/a-1214-6718
DO - 10.1055/a-1214-6718
M3 - Article
C2 - 32731264
AN - SCOPUS:85092253500
SN - 0032-0943
VL - 86
SP - 1345
EP - 1352
JO - Planta Medica
JF - Planta Medica
IS - 18
ER -