Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised rats

Introduction: The renal renin–angiotensin system (RAS) and the ultrasensitive energy sensor AMP-activated protein kinase (AMPK) have been implicated in normal and aberrant states of the kidney, but interaction between the RAS and AMPK remains unknown. Methods: Ninety-six rats were stratified into fo...

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Main Authors: Ke-Ke Yang, Yi Sui, Hui-Rong Zhou, Jian Shen, Ning Tan, Yan-Mei Huang, Sha-Sha LI, Yan-Hong Pan, Xiao-Xi Zhang, Hai-Lu Zhao
Format: Article
Language:English
Published: SAGE Publications 2016-10-01
Series:Journal of the Renin-Angiotensin-Aldosterone System
Online Access:https://doi.org/10.1177/1470320316673231
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author Ke-Ke Yang
Yi Sui
Hui-Rong Zhou
Jian Shen
Ning Tan
Yan-Mei Huang
Sha-Sha LI
Yan-Hong Pan
Xiao-Xi Zhang
Hai-Lu Zhao
author_facet Ke-Ke Yang
Yi Sui
Hui-Rong Zhou
Jian Shen
Ning Tan
Yan-Mei Huang
Sha-Sha LI
Yan-Hong Pan
Xiao-Xi Zhang
Hai-Lu Zhao
author_sort Ke-Ke Yang
collection DOAJ
description Introduction: The renal renin–angiotensin system (RAS) and the ultrasensitive energy sensor AMP-activated protein kinase (AMPK) have been implicated in normal and aberrant states of the kidney, but interaction between the RAS and AMPK remains unknown. Methods: Ninety-six rats were stratified into four groups: sham, uninephrectomised, uninephrectomised rats treated with the angiotensin-converting enzyme inhibitor lisinopril or the angiotensin receptor blocker losartan. Histopathological examination at 9 months post-operation and biochemical measurements at 3, 6 and 9 months were performed for changes in renal structure and function. The expression of AMPK and angiotensin II at 9 months was detected by immunofluorescence microscopy and western blot. Results: Compared with sham rats, uninephrectomised rats demonstrated progressive glomerulosclerosis, tubular atrophy with cast formation and chronic inflammatory infiltration, in parallel to elevated serum urea, creatinine, urine total protein to creatinine ratio and reduced serum albumin. Overexpression of angiotensin II coexisted with a 85.6% reduction of phosphorylated to total AMPK ratio in the remnant kidney of uninephrectomised rats. RAS blockade by the angiotensin-converting enzyme inhibitor or angiotensin receptor blocker substantially normalised AMPK expression, morphological and functional changes of the remnant kidney. Conclusions: Uninephrectomy-induced RAS activation and AMPK inhibition in the remnant kidney could be substantially corrected by RAS blockade, suggesting a cross-talk between AMPK and RAS components in uninephrectomised rats.
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spelling doaj.art-ac6003e6b86447ac9ec93cf6b3acd9fe2024-03-03T03:42:17ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1752-89762016-10-011710.1177/147032031667323110.1177_1470320316673231Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised ratsKe-Ke Yang0Yi Sui1Hui-Rong Zhou2Jian Shen3Ning Tan4Yan-Mei Huang5Sha-Sha LI6Yan-Hong Pan7Xiao-Xi Zhang8Hai-Lu Zhao9Department of Laboratory, The Second Affiliated Hospital of Nantong University, ChinaCenter for Diabetic Systems Medicine, Guilin Medical University, ChinaDepartment of Surgical Pathology, Shenzhen Hospital of Southern Medical University, ChinaCenter for Diabetic Systems Medicine, Guilin Medical University, ChinaCentral Laboratory of Core Facilities, Guilin Medical University, ChinaCenter for Diabetic Systems Medicine, Guilin Medical University, ChinaCenter for Diabetic Systems Medicine, Guilin Medical University, ChinaCenter for Diabetic Systems Medicine, Guilin Medical University, ChinaCenter for Diabetic Systems Medicine, Guilin Medical University, ChinaCenter for Diabetic Systems Medicine, Guilin Medical University, ChinaIntroduction: The renal renin–angiotensin system (RAS) and the ultrasensitive energy sensor AMP-activated protein kinase (AMPK) have been implicated in normal and aberrant states of the kidney, but interaction between the RAS and AMPK remains unknown. Methods: Ninety-six rats were stratified into four groups: sham, uninephrectomised, uninephrectomised rats treated with the angiotensin-converting enzyme inhibitor lisinopril or the angiotensin receptor blocker losartan. Histopathological examination at 9 months post-operation and biochemical measurements at 3, 6 and 9 months were performed for changes in renal structure and function. The expression of AMPK and angiotensin II at 9 months was detected by immunofluorescence microscopy and western blot. Results: Compared with sham rats, uninephrectomised rats demonstrated progressive glomerulosclerosis, tubular atrophy with cast formation and chronic inflammatory infiltration, in parallel to elevated serum urea, creatinine, urine total protein to creatinine ratio and reduced serum albumin. Overexpression of angiotensin II coexisted with a 85.6% reduction of phosphorylated to total AMPK ratio in the remnant kidney of uninephrectomised rats. RAS blockade by the angiotensin-converting enzyme inhibitor or angiotensin receptor blocker substantially normalised AMPK expression, morphological and functional changes of the remnant kidney. Conclusions: Uninephrectomy-induced RAS activation and AMPK inhibition in the remnant kidney could be substantially corrected by RAS blockade, suggesting a cross-talk between AMPK and RAS components in uninephrectomised rats.https://doi.org/10.1177/1470320316673231
spellingShingle Ke-Ke Yang
Yi Sui
Hui-Rong Zhou
Jian Shen
Ning Tan
Yan-Mei Huang
Sha-Sha LI
Yan-Hong Pan
Xiao-Xi Zhang
Hai-Lu Zhao
Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised rats
Journal of the Renin-Angiotensin-Aldosterone System
title Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised rats
title_full Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised rats
title_fullStr Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised rats
title_full_unstemmed Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised rats
title_short Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised rats
title_sort cross talk between amp activated protein kinase and renin angiotensin system in uninephrectomised rats
url https://doi.org/10.1177/1470320316673231
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