Protease-activated receptor-1-induced calcium signaling in gingival fibroblasts is mediated by sarcoplasmic reticulum calcium release and extracellular calcium influx

Jiiang Huei Jeng, Chiu Po Chan, Hui Lin Wu, Yuan Soon Ho, Jang Jaer Lee, Chang Huei Liao, Yu Kaung Chang, Hsiao Hua Chang, Yi Jane Chen, Pey Jey Perng, Mei Chi Chang

研究成果: 雜誌貢獻文章

18 引文 (Scopus)

摘要

Thrombin is a serine protease activated during injury and inflammation. Thrombin and other proteases generated by periodontal pathogens affect the behavior of periodontal cells via activation of protease-activated receptors (PARs). We noted that thrombin and PAR-1 agonist peptide stimulated intracellular calcium levels ([Ca2+]i) of gingival fibroblasts (GF). This increase of [Ca2+]i was inhibited by EGTA and verapamil. U73122 and neomycin inhibited thrombin- and PAR-1-induced [Ca2+]i. Furthermore, 2-APB (75-100 μM, inositol triphosphate [IP3] receptor antagonist), thapsigargin (1 μM), SKF-96365 (200 μM) and W7 (50 and 100 μM) also suppressed the PAR-1- and thrombin-induced [Ca2+]i. However, H7 (100, 200 μM) and ryanodine showed little effects. Blocking Ca2+ efflux from mitochondria by CGP37157 (50, 100 μM) inhibited both thrombin- and PAR-1-induced [Ca2+]i. Thrombin induced the IP3 production of GF within 30-seconds of exposure, which was inhibited by U73122. These results indicate that mitochondrial calcium efflux and calcium-calmodulin pathways are related to thrombin and PAR-1 induced [Ca2+]i in GF. Thrombin-induced [Ca2+]i of GF is mainly due to PAR-1 activation, extracellular calcium influx via L-type calcium channel, PLC activation, then IP3 binding to IP3 receptor in sarcoplasmic reticulum, which leads to intracellular calcium release and subsequently alters cell membrane capacitative calcium entry.

原文英語
頁(從 - 到)731-740
頁數10
期刊Cellular Signalling
16
發行號6
DOIs
出版狀態已發佈 - 六月 2004

指紋

PAR-1 Receptor
Calcium Signaling
Sarcoplasmic Reticulum
Thrombin
Fibroblasts
Calcium
Inositol 1,4,5-Trisphosphate Receptors
1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
Proteinase-Activated Receptors
Ryanodine
L-Type Calcium Channels
Thapsigargin
Neomycin
Egtazic Acid
Serine Proteases
Calmodulin
Verapamil
Mitochondria
Peptide Hydrolases
Cell Membrane

ASJC Scopus subject areas

  • Cell Biology

引用此文

Protease-activated receptor-1-induced calcium signaling in gingival fibroblasts is mediated by sarcoplasmic reticulum calcium release and extracellular calcium influx. / Jeng, Jiiang Huei; Chan, Chiu Po; Wu, Hui Lin; Ho, Yuan Soon; Lee, Jang Jaer; Liao, Chang Huei; Chang, Yu Kaung; Chang, Hsiao Hua; Chen, Yi Jane; Perng, Pey Jey; Chang, Mei Chi.

於: Cellular Signalling, 卷 16, 編號 6, 06.2004, p. 731-740.

研究成果: 雜誌貢獻文章

Jeng, Jiiang Huei ; Chan, Chiu Po ; Wu, Hui Lin ; Ho, Yuan Soon ; Lee, Jang Jaer ; Liao, Chang Huei ; Chang, Yu Kaung ; Chang, Hsiao Hua ; Chen, Yi Jane ; Perng, Pey Jey ; Chang, Mei Chi. / Protease-activated receptor-1-induced calcium signaling in gingival fibroblasts is mediated by sarcoplasmic reticulum calcium release and extracellular calcium influx. 於: Cellular Signalling. 2004 ; 卷 16, 編號 6. 頁 731-740.
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title = "Protease-activated receptor-1-induced calcium signaling in gingival fibroblasts is mediated by sarcoplasmic reticulum calcium release and extracellular calcium influx",
abstract = "Thrombin is a serine protease activated during injury and inflammation. Thrombin and other proteases generated by periodontal pathogens affect the behavior of periodontal cells via activation of protease-activated receptors (PARs). We noted that thrombin and PAR-1 agonist peptide stimulated intracellular calcium levels ([Ca2+]i) of gingival fibroblasts (GF). This increase of [Ca2+]i was inhibited by EGTA and verapamil. U73122 and neomycin inhibited thrombin- and PAR-1-induced [Ca2+]i. Furthermore, 2-APB (75-100 μM, inositol triphosphate [IP3] receptor antagonist), thapsigargin (1 μM), SKF-96365 (200 μM) and W7 (50 and 100 μM) also suppressed the PAR-1- and thrombin-induced [Ca2+]i. However, H7 (100, 200 μM) and ryanodine showed little effects. Blocking Ca2+ efflux from mitochondria by CGP37157 (50, 100 μM) inhibited both thrombin- and PAR-1-induced [Ca2+]i. Thrombin induced the IP3 production of GF within 30-seconds of exposure, which was inhibited by U73122. These results indicate that mitochondrial calcium efflux and calcium-calmodulin pathways are related to thrombin and PAR-1 induced [Ca2+]i in GF. Thrombin-induced [Ca2+]i of GF is mainly due to PAR-1 activation, extracellular calcium influx via L-type calcium channel, PLC activation, then IP3 binding to IP3 receptor in sarcoplasmic reticulum, which leads to intracellular calcium release and subsequently alters cell membrane capacitative calcium entry.",
keywords = "BAPTA/AM, Calcium channel, Calcium mobilization, Calcium-calmodulin, Capacitative calcium entry, Gingival fibroblast, Inositol triphosphate receptor, Phospholipase C, Protease-activated receptors",
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T1 - Protease-activated receptor-1-induced calcium signaling in gingival fibroblasts is mediated by sarcoplasmic reticulum calcium release and extracellular calcium influx

AU - Jeng, Jiiang Huei

AU - Chan, Chiu Po

AU - Wu, Hui Lin

AU - Ho, Yuan Soon

AU - Lee, Jang Jaer

AU - Liao, Chang Huei

AU - Chang, Yu Kaung

AU - Chang, Hsiao Hua

AU - Chen, Yi Jane

AU - Perng, Pey Jey

AU - Chang, Mei Chi

PY - 2004/6

Y1 - 2004/6

N2 - Thrombin is a serine protease activated during injury and inflammation. Thrombin and other proteases generated by periodontal pathogens affect the behavior of periodontal cells via activation of protease-activated receptors (PARs). We noted that thrombin and PAR-1 agonist peptide stimulated intracellular calcium levels ([Ca2+]i) of gingival fibroblasts (GF). This increase of [Ca2+]i was inhibited by EGTA and verapamil. U73122 and neomycin inhibited thrombin- and PAR-1-induced [Ca2+]i. Furthermore, 2-APB (75-100 μM, inositol triphosphate [IP3] receptor antagonist), thapsigargin (1 μM), SKF-96365 (200 μM) and W7 (50 and 100 μM) also suppressed the PAR-1- and thrombin-induced [Ca2+]i. However, H7 (100, 200 μM) and ryanodine showed little effects. Blocking Ca2+ efflux from mitochondria by CGP37157 (50, 100 μM) inhibited both thrombin- and PAR-1-induced [Ca2+]i. Thrombin induced the IP3 production of GF within 30-seconds of exposure, which was inhibited by U73122. These results indicate that mitochondrial calcium efflux and calcium-calmodulin pathways are related to thrombin and PAR-1 induced [Ca2+]i in GF. Thrombin-induced [Ca2+]i of GF is mainly due to PAR-1 activation, extracellular calcium influx via L-type calcium channel, PLC activation, then IP3 binding to IP3 receptor in sarcoplasmic reticulum, which leads to intracellular calcium release and subsequently alters cell membrane capacitative calcium entry.

AB - Thrombin is a serine protease activated during injury and inflammation. Thrombin and other proteases generated by periodontal pathogens affect the behavior of periodontal cells via activation of protease-activated receptors (PARs). We noted that thrombin and PAR-1 agonist peptide stimulated intracellular calcium levels ([Ca2+]i) of gingival fibroblasts (GF). This increase of [Ca2+]i was inhibited by EGTA and verapamil. U73122 and neomycin inhibited thrombin- and PAR-1-induced [Ca2+]i. Furthermore, 2-APB (75-100 μM, inositol triphosphate [IP3] receptor antagonist), thapsigargin (1 μM), SKF-96365 (200 μM) and W7 (50 and 100 μM) also suppressed the PAR-1- and thrombin-induced [Ca2+]i. However, H7 (100, 200 μM) and ryanodine showed little effects. Blocking Ca2+ efflux from mitochondria by CGP37157 (50, 100 μM) inhibited both thrombin- and PAR-1-induced [Ca2+]i. Thrombin induced the IP3 production of GF within 30-seconds of exposure, which was inhibited by U73122. These results indicate that mitochondrial calcium efflux and calcium-calmodulin pathways are related to thrombin and PAR-1 induced [Ca2+]i in GF. Thrombin-induced [Ca2+]i of GF is mainly due to PAR-1 activation, extracellular calcium influx via L-type calcium channel, PLC activation, then IP3 binding to IP3 receptor in sarcoplasmic reticulum, which leads to intracellular calcium release and subsequently alters cell membrane capacitative calcium entry.

KW - BAPTA/AM

KW - Calcium channel

KW - Calcium mobilization

KW - Calcium-calmodulin

KW - Capacitative calcium entry

KW - Gingival fibroblast

KW - Inositol triphosphate receptor

KW - Phospholipase C

KW - Protease-activated receptors

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U2 - 10.1016/j.cellsig.2003.11.008

DO - 10.1016/j.cellsig.2003.11.008

M3 - Article

C2 - 15093614

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