Bradykinin-stimulated p42/p44 MAPK activation associated with cell proliferation in corneal keratocytes

Ching Yi Cheng; Samuel C.M. Huang; Li Der Hsiao; Chi Chin Sun; Mei Jie Jou; Chuen Mao Yang

doi:10.1016/j.cellsig.2003.09.005

Bradykinin-stimulated p42/p44 MAPK activation associated with cell proliferation in corneal keratocytes

Ching Yi Cheng, Samuel C.M. Huang, Li Der Hsiao, Chi Chin Sun, Mei Jie Jou, Chuen Mao Yang^*

^*Corresponding author for this work

Chang Gung University

Research output: Contribution to journal › Journal Article › peer-review

11 Scopus citations

Abstract

Bradykinin (BK) is released into the tear-film in ocular allergic patients. BK has been shown to exert mitogenic effects on several cell types. However, the mechanisms underlying its action on corneal keratocytes (CKs) were largely unknown. This study was to investigate the mitogenic effect of BK on rabbit CKs linked to activation of p42/p44 mitogen-activated protein kinase (MAPK), assessed by [³H]thymidine incorporation and Western blotting analysis, respectively. BK stimulated [³H]thymidine incorporation and p42/p44 MAPK phosphorylation in a time- and concentration-dependent manner. Pretreatment with pertussis toxin attenuated the BK-induced responses. BK-stimulated responses were attenuated by inhibitors of selective B ₂ receptor (Hoe 140), phosphatidylinositol (PI)-PLC (U73122), an intracellular Ca²⁺chelator (BAPTA/AM), PKC (GF109203X), tyrosine kinase (genistein), and MEK1/2 (PD98059). BK also stimulated translocation of p42/p44 MAPK into nucleus and led to expression of c-fos and c-jun in CKs. These results demonstrate that in CKs, BK-stimulated phosphorylation of p42/p44 MAPK is mediated through the activation of BK B₂ receptors and leads to cell proliferation.

Original language	English
Pages (from-to)	535-549
Number of pages	15
Journal	Cellular Signalling
Volume	16
Issue number	5
DOIs	https://doi.org/10.1016/j.cellsig.2003.09.005
State	Published - 05 2004

Keywords

Bradykinin receptor
MEK
Mitogen-activated protein kinase
Protein kinase C
Tyrosine kinase

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title = "Bradykinin-stimulated p42/p44 MAPK activation associated with cell proliferation in corneal keratocytes",

abstract = "Bradykinin (BK) is released into the tear-film in ocular allergic patients. BK has been shown to exert mitogenic effects on several cell types. However, the mechanisms underlying its action on corneal keratocytes (CKs) were largely unknown. This study was to investigate the mitogenic effect of BK on rabbit CKs linked to activation of p42/p44 mitogen-activated protein kinase (MAPK), assessed by [3H]thymidine incorporation and Western blotting analysis, respectively. BK stimulated [3H]thymidine incorporation and p42/p44 MAPK phosphorylation in a time- and concentration-dependent manner. Pretreatment with pertussis toxin attenuated the BK-induced responses. BK-stimulated responses were attenuated by inhibitors of selective B 2 receptor (Hoe 140), phosphatidylinositol (PI)-PLC (U73122), an intracellular Ca2+chelator (BAPTA/AM), PKC (GF109203X), tyrosine kinase (genistein), and MEK1/2 (PD98059). BK also stimulated translocation of p42/p44 MAPK into nucleus and led to expression of c-fos and c-jun in CKs. These results demonstrate that in CKs, BK-stimulated phosphorylation of p42/p44 MAPK is mediated through the activation of BK B2 receptors and leads to cell proliferation.",

keywords = "Bradykinin receptor, MEK, Mitogen-activated protein kinase, Protein kinase C, Tyrosine kinase",

author = "Cheng, {Ching Yi} and Huang, {Samuel C.M.} and Hsiao, {Li Der} and Sun, {Chi Chin} and Jou, {Mei Jie} and Yang, {Chuen Mao}",

year = "2004",

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T1 - Bradykinin-stimulated p42/p44 MAPK activation associated with cell proliferation in corneal keratocytes

AU - Cheng, Ching Yi

AU - Huang, Samuel C.M.

AU - Hsiao, Li Der

AU - Sun, Chi Chin

AU - Jou, Mei Jie

AU - Yang, Chuen Mao

PY - 2004/5

Y1 - 2004/5

N2 - Bradykinin (BK) is released into the tear-film in ocular allergic patients. BK has been shown to exert mitogenic effects on several cell types. However, the mechanisms underlying its action on corneal keratocytes (CKs) were largely unknown. This study was to investigate the mitogenic effect of BK on rabbit CKs linked to activation of p42/p44 mitogen-activated protein kinase (MAPK), assessed by [3H]thymidine incorporation and Western blotting analysis, respectively. BK stimulated [3H]thymidine incorporation and p42/p44 MAPK phosphorylation in a time- and concentration-dependent manner. Pretreatment with pertussis toxin attenuated the BK-induced responses. BK-stimulated responses were attenuated by inhibitors of selective B 2 receptor (Hoe 140), phosphatidylinositol (PI)-PLC (U73122), an intracellular Ca2+chelator (BAPTA/AM), PKC (GF109203X), tyrosine kinase (genistein), and MEK1/2 (PD98059). BK also stimulated translocation of p42/p44 MAPK into nucleus and led to expression of c-fos and c-jun in CKs. These results demonstrate that in CKs, BK-stimulated phosphorylation of p42/p44 MAPK is mediated through the activation of BK B2 receptors and leads to cell proliferation.

AB - Bradykinin (BK) is released into the tear-film in ocular allergic patients. BK has been shown to exert mitogenic effects on several cell types. However, the mechanisms underlying its action on corneal keratocytes (CKs) were largely unknown. This study was to investigate the mitogenic effect of BK on rabbit CKs linked to activation of p42/p44 mitogen-activated protein kinase (MAPK), assessed by [3H]thymidine incorporation and Western blotting analysis, respectively. BK stimulated [3H]thymidine incorporation and p42/p44 MAPK phosphorylation in a time- and concentration-dependent manner. Pretreatment with pertussis toxin attenuated the BK-induced responses. BK-stimulated responses were attenuated by inhibitors of selective B 2 receptor (Hoe 140), phosphatidylinositol (PI)-PLC (U73122), an intracellular Ca2+chelator (BAPTA/AM), PKC (GF109203X), tyrosine kinase (genistein), and MEK1/2 (PD98059). BK also stimulated translocation of p42/p44 MAPK into nucleus and led to expression of c-fos and c-jun in CKs. These results demonstrate that in CKs, BK-stimulated phosphorylation of p42/p44 MAPK is mediated through the activation of BK B2 receptors and leads to cell proliferation.

KW - Bradykinin receptor

KW - MEK

KW - Mitogen-activated protein kinase

KW - Protein kinase C

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JO - Cellular Signalling

JF - Cellular Signalling

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ER -

Bradykinin-stimulated p42/p44 MAPK activation associated with cell proliferation in corneal keratocytes

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Keywords

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