Protein kinase Cb mediates downregulated expression of glucagon-like peptide-1receptor in hypertensive rat renal arteries

Limei Liu; Jian Liu; Yuansheng Gao; Chi Fai Ng; Xiaoxing Yu; Dou Dou; Yu Huang

doi:10.1097/HJH.0000000000000480

Protein kinase Cb mediates downregulated expression of glucagon-like peptide-1receptor in hypertensive rat renal arteries

Limei Liu^*, Jian Liu, Yuansheng Gao, Chi Fai Ng, Xiaoxing Yu, Dou Dou, Yu Huang

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

13 Citations (Scopus)

Abstract

Objective: Glucagon-like peptide-1 (GLP-1) exerts its actions via activating GLP-1 receptor (GLP-1R). Our previous study showed a reduced GLP-1R expression in spontaneously hypertensive rat (SHR) renal arteries. The present study investigated the mechanisms underlying GLP- 1R downregulation in hypertension. Methods: Intrarenal arteries of normotensive Wistar-Kyoto rat (WKY) and SHR were suspended in the myograph for force measurement. GLP-1R expression was evaluated by both immunofluorescence and western blotting. Protein kinase Ca (PKCa), PKCb, PKCd, and total PKC levels were assayed by western blotting. Results: Immunofluorescence revealed reduced GLP-1R level in SHR renal arteries compared with WKY renal arteries. GLP-1R agonist exendin-4 induced concentrationdependent relaxations in WKY arteries, which mainly depended on the presence of endothelium. GLP-1R antagonist exendin 9-39 inhibited this relaxation in WKY arteries, whereas the relaxations were significantly less in SHR arteries. Ex-vivo treatment with PKC inhibitor GFX, PKCa and PKCb inhibitor Go 6976, and PKCb inhibitor hispidin but not PKCd inhibitor rottlerin improved the impaired relaxations and restored the diminished GLP-1R expression in SHR arteries. Furthermore, PKCb level was greater in SHR than WKY arteries, with no difference in PKCa, PKCd, or total PKC expressions between two rat strains. Treatment with PKC-activating agent phorbol-12- myristate-13-acetate attenuated exendin-4-induced relaxations and reduced GLP-1R expression in WKY arteries, which were reversed by GFX, Go 6976, or hispidin. More relevantly, immunofluorescence of human renal arteries also showed a reduced GLP-1R level in hypertensive patients. Conclusion: The present results provide novel evidence that the reduced GLP-1R expression in SHR renal arteries is most likely mediated through PKCb upregulation; the latter probably contributes to the impaired GLP-1Rmediated vasorelaxations in hypertension.

Original language	English
Pages (from-to)	784-790
Journal	Journal of Hypertension
Volume	33
Issue number	4
DOIs	https://doi.org/10.1097/HJH.0000000000000480
Publication status	Published - 1 Apr 2015
Externally published	Yes

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Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

Glucagon-like peptide-1 receptor
Hypertension
Protein kinase C
Renal artery

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10.1097/HJH.0000000000000480

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@article{2f8d44d2b3bb44d6a272fb3e5fa00e79,

title = "Protein kinase Cb mediates downregulated expression of glucagon-like peptide-1receptor in hypertensive rat renal arteries",

abstract = "Objective: Glucagon-like peptide-1 (GLP-1) exerts its actions via activating GLP-1 receptor (GLP-1R). Our previous study showed a reduced GLP-1R expression in spontaneously hypertensive rat (SHR) renal arteries. The present study investigated the mechanisms underlying GLP- 1R downregulation in hypertension. Methods: Intrarenal arteries of normotensive Wistar-Kyoto rat (WKY) and SHR were suspended in the myograph for force measurement. GLP-1R expression was evaluated by both immunofluorescence and western blotting. Protein kinase Ca (PKCa), PKCb, PKCd, and total PKC levels were assayed by western blotting. Results: Immunofluorescence revealed reduced GLP-1R level in SHR renal arteries compared with WKY renal arteries. GLP-1R agonist exendin-4 induced concentrationdependent relaxations in WKY arteries, which mainly depended on the presence of endothelium. GLP-1R antagonist exendin 9-39 inhibited this relaxation in WKY arteries, whereas the relaxations were significantly less in SHR arteries. Ex-vivo treatment with PKC inhibitor GFX, PKCa and PKCb inhibitor Go 6976, and PKCb inhibitor hispidin but not PKCd inhibitor rottlerin improved the impaired relaxations and restored the diminished GLP-1R expression in SHR arteries. Furthermore, PKCb level was greater in SHR than WKY arteries, with no difference in PKCa, PKCd, or total PKC expressions between two rat strains. Treatment with PKC-activating agent phorbol-12- myristate-13-acetate attenuated exendin-4-induced relaxations and reduced GLP-1R expression in WKY arteries, which were reversed by GFX, Go 6976, or hispidin. More relevantly, immunofluorescence of human renal arteries also showed a reduced GLP-1R level in hypertensive patients. Conclusion: The present results provide novel evidence that the reduced GLP-1R expression in SHR renal arteries is most likely mediated through PKCb upregulation; the latter probably contributes to the impaired GLP-1Rmediated vasorelaxations in hypertension.",

keywords = "Glucagon-like peptide-1 receptor, Hypertension, Protein kinase C, Renal artery",

author = "Limei Liu and Jian Liu and Yuansheng Gao and Ng, {Chi Fai} and Xiaoxing Yu and Dou Dou and Yu Huang",

note = "Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].",

year = "2015",

month = apr,

day = "1",

doi = "10.1097/HJH.0000000000000480",

language = "English",

volume = "33",

pages = "784--790",

journal = "Journal of Hypertension",

issn = "0263-6352",

publisher = "Lippincott Williams & Wilkins",

number = "4",

}

TY - JOUR

T1 - Protein kinase Cb mediates downregulated expression of glucagon-like peptide-1receptor in hypertensive rat renal arteries

AU - Liu, Limei

AU - Liu, Jian

AU - Gao, Yuansheng

AU - Ng, Chi Fai

AU - Yu, Xiaoxing

AU - Dou, Dou

AU - Huang, Yu

N1 - Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Objective: Glucagon-like peptide-1 (GLP-1) exerts its actions via activating GLP-1 receptor (GLP-1R). Our previous study showed a reduced GLP-1R expression in spontaneously hypertensive rat (SHR) renal arteries. The present study investigated the mechanisms underlying GLP- 1R downregulation in hypertension. Methods: Intrarenal arteries of normotensive Wistar-Kyoto rat (WKY) and SHR were suspended in the myograph for force measurement. GLP-1R expression was evaluated by both immunofluorescence and western blotting. Protein kinase Ca (PKCa), PKCb, PKCd, and total PKC levels were assayed by western blotting. Results: Immunofluorescence revealed reduced GLP-1R level in SHR renal arteries compared with WKY renal arteries. GLP-1R agonist exendin-4 induced concentrationdependent relaxations in WKY arteries, which mainly depended on the presence of endothelium. GLP-1R antagonist exendin 9-39 inhibited this relaxation in WKY arteries, whereas the relaxations were significantly less in SHR arteries. Ex-vivo treatment with PKC inhibitor GFX, PKCa and PKCb inhibitor Go 6976, and PKCb inhibitor hispidin but not PKCd inhibitor rottlerin improved the impaired relaxations and restored the diminished GLP-1R expression in SHR arteries. Furthermore, PKCb level was greater in SHR than WKY arteries, with no difference in PKCa, PKCd, or total PKC expressions between two rat strains. Treatment with PKC-activating agent phorbol-12- myristate-13-acetate attenuated exendin-4-induced relaxations and reduced GLP-1R expression in WKY arteries, which were reversed by GFX, Go 6976, or hispidin. More relevantly, immunofluorescence of human renal arteries also showed a reduced GLP-1R level in hypertensive patients. Conclusion: The present results provide novel evidence that the reduced GLP-1R expression in SHR renal arteries is most likely mediated through PKCb upregulation; the latter probably contributes to the impaired GLP-1Rmediated vasorelaxations in hypertension.

AB - Objective: Glucagon-like peptide-1 (GLP-1) exerts its actions via activating GLP-1 receptor (GLP-1R). Our previous study showed a reduced GLP-1R expression in spontaneously hypertensive rat (SHR) renal arteries. The present study investigated the mechanisms underlying GLP- 1R downregulation in hypertension. Methods: Intrarenal arteries of normotensive Wistar-Kyoto rat (WKY) and SHR were suspended in the myograph for force measurement. GLP-1R expression was evaluated by both immunofluorescence and western blotting. Protein kinase Ca (PKCa), PKCb, PKCd, and total PKC levels were assayed by western blotting. Results: Immunofluorescence revealed reduced GLP-1R level in SHR renal arteries compared with WKY renal arteries. GLP-1R agonist exendin-4 induced concentrationdependent relaxations in WKY arteries, which mainly depended on the presence of endothelium. GLP-1R antagonist exendin 9-39 inhibited this relaxation in WKY arteries, whereas the relaxations were significantly less in SHR arteries. Ex-vivo treatment with PKC inhibitor GFX, PKCa and PKCb inhibitor Go 6976, and PKCb inhibitor hispidin but not PKCd inhibitor rottlerin improved the impaired relaxations and restored the diminished GLP-1R expression in SHR arteries. Furthermore, PKCb level was greater in SHR than WKY arteries, with no difference in PKCa, PKCd, or total PKC expressions between two rat strains. Treatment with PKC-activating agent phorbol-12- myristate-13-acetate attenuated exendin-4-induced relaxations and reduced GLP-1R expression in WKY arteries, which were reversed by GFX, Go 6976, or hispidin. More relevantly, immunofluorescence of human renal arteries also showed a reduced GLP-1R level in hypertensive patients. Conclusion: The present results provide novel evidence that the reduced GLP-1R expression in SHR renal arteries is most likely mediated through PKCb upregulation; the latter probably contributes to the impaired GLP-1Rmediated vasorelaxations in hypertension.

KW - Glucagon-like peptide-1 receptor

KW - Hypertension

KW - Protein kinase C

KW - Renal artery

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U2 - 10.1097/HJH.0000000000000480

DO - 10.1097/HJH.0000000000000480

M3 - RGC 21 - Publication in refereed journal

C2 - 25915883

SN - 0263-6352

VL - 33

SP - 784

EP - 790

JO - Journal of Hypertension

JF - Journal of Hypertension

IS - 4

ER -

Protein kinase Cb mediates downregulated expression of glucagon-like peptide-1receptor in hypertensive rat renal arteries

Abstract

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