|
KMID : 0359920140330010026
|
|
Korean Journal of Nephrology
2014 Volume.33 No. 1 p.26 ~ p.32
|
|
|
Diabetic conditions modulate the adenosine monophosphate-activated protein kinase of podocytes
|
|
Ha Tae-Sun
Park Hye-Young
Nam Ja-Ae
Han Gi-Dong
|
|
|
Abstract
|
|
|
Background: Adenosine monophosphate-activated protein kinases (AMPKs), as a sensor of cellular energy status, have been known to play an important role in the pathophysiology of diabetes and its complications. Because AMPKs are known to be expressed in podocytes, it is possible that podocyte AMPKs could be an important contributing factor in the development of diabetic proteinuria. We investigated the roles of AMPKs in the pathological changes in podocytes induced by high-glucose (HG) and advanced glycosylation end products (AGEs) in diabetic proteinuria.
Methods: We prepared streptozotocin-induced diabetic renal tissues and culturedrat and mouse podocytes under diabetic conditions with AMPK-modulating agents.The changes in AMPKα were analyzed with confocal imaging and Western blotting under the following conditions: (1) normal glucose (5mM, ¼control); (2) HG (30mM); (3) AGE-added; or (4) HG plus AGE-added.
Results: The density of glomerularphospho-AMPKa in experimental diabetic nephropathy decreased as a function of the diabetic duration. Diabetic conditions
including HG and AGE changed the localization of phospho-AMPKa from peripheral cytoplasm to internal cytoplasm and peri- and intranuclear areas in podocytes. HG reduced the AMPKa (Thr172) phosphorylation of rat podocytes, and similarly, AGEs reduced the AMPKa (Thr172) phosphorylation of mouse podocytes. The distributional and quantitative changes in phospho-AMPKa caused by diabetic conditions were preventable using AMPK activators, metformin, and 5-aminoimidazole-4-carboxamide-1b-riboside.
Conclusion: We suggest that diabetic conditions induce the relocation and suppression of podocyte AMPKα, which would be a suggestive mechanism in diabetic podocyte injury.
|
|
|
KEYWORD
|
|
|
Adenosine monophosphate-activated, Advancedglycosylationendproducts, Diabetic nephropathy, Podocyte
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|