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Angiotensin II suppresses adenosine monophosphate-activated protein kinase of podocytes via angiotensin II type 1 receptor and mitogen-activated protein kinase signaling
- Source :
- Clinical and Experimental Nephrology. 17:16-23
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- Adenosine monophosphate (AMP)-activated protein kinase (AMPK), as a sensor of cellular energy status, has been known to play an important role in the pathophysiology of diabetes and its complications. As AMPK is also expressed in podocytes, it is possible that podocyte AMPK would be an important contributing factor in the development of diabetic proteinuria. We investigated the roles of AMPK in the pathological changes of podocytes induced by angiotensin II (Ang II), a major injury inducer in diabetic proteinuria. Mouse podocytes were incubated in media containing various concentrations of Ang II and AMPK-modulating agents. The changes of AMPKα were analyzed by confocal imaging and Western blotting in response to Ang II. Ang II changed the localization of AMPKα from peripheral cytoplasm into internal cytoplasm and peri- and intranuclear areas in podocytes. Ang II also reduced AMPKα (Thr172) phosphorylation in time- and dose-sensitive manners. In particular, 10−7 M Ang II reduced phospho-AMPKα significantly and continuously at 6, 24, and 48 h. AMPK activators, metformin and 5-aminoimidazole-4-carboxamide-1β-riboside, restored the suppressed AMPKα (Thr172) phosphorylation. Losartan, an Ang II type 1 receptor antagonist, also recovered the suppression and the mal-localization of AMPKα, which were induced by Ang II. PD98059, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor, also restored the AMPKα (Thr172) phosphorylation suppressed by Ang II. We suggest that Ang II induces the relocation and suppression of podocyte AMPKα via Ang II type 1 receptor and MAPK signaling pathway, which would be an important mechanism in Ang II-induced podocyte injury.
- Subjects :
- MAPK/ERK pathway
Angiotensin receptor
medicine.medical_specialty
Time Factors
MAP Kinase Signaling System
Physiology
Blotting, Western
Enzyme Activators
AMP-Activated Protein Kinases
Mitogen-activated protein kinase kinase
Receptor, Angiotensin, Type 1
Cell Line
Mice
Physiology (medical)
Internal medicine
medicine
Animals
Phosphorylation
Protein kinase A
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinase Kinases
Microscopy, Confocal
Angiotensin II receptor type 1
Dose-Response Relationship, Drug
Podocytes
business.industry
Angiotensin II
AMPK
Enzyme Activation
Protein Transport
Endocrinology
Losartan
Nephrology
business
Angiotensin II Type 1 Receptor Blockers
hormones, hormone substitutes, and hormone antagonists
medicine.drug
Subjects
Details
- ISSN :
- 14377799 and 13421751
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Clinical and Experimental Nephrology
- Accession number :
- edsair.doi.dedup.....9c233ac655ff8abaf0380559aae2dbd9