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Activation of local aldosterone system within podocytes is involved in apoptosis under diabetic conditions

Authors
 Sun Ha Lee  ;  Tae-Hyun Yoo  ;  Bo-Young Nam  ;  Dong Ki Kim  ;  Jin Ji Li  ;  Dong-Sub Jung  ;  Seung-Jae Kwak  ;  Dong-Ryeol Ryu  ;  Seung Hyeok Han  ;  Jung Eun Lee  ;  Sung Jin Moon  ;  Dae Suk Han  ;  Shin-Wook Kang 
Citation
 AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, Vol.297(5) : 1381-90, 2009 
Journal Title
 AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 
ISSN
 1931-857X 
Issue Date
2009
MeSH
11-beta-Hydroxysteroid Dehydrogenase Type 2/biosynthesis ; 11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics ; Aldosterone/physiology* ; Animals ; Apoptosis/physiology* ; Apoptosis Regulatory Proteins/biosynthesis ; Apoptosis Regulatory Proteins/genetics ; Benzimidazoles ; Blotting, Western ; Caspase 3/biosynthesis ; Caspase 3/genetics ; Cell Count ; Cells, Cultured ; Cytochrome P-450 CYP11B2/biosynthesis ; Cytochrome P-450 CYP11B2/genetics ; Diabetes Mellitus, Experimental/pathology* ; Fluorescent Antibody Technique ; Fluorescent Dyes ; In Situ Nick-End Labeling ; Kidney/pathology ; Kidney Glomerulus/metabolism ; Male ; Podocytes/physiology* ; Rats ; Rats, Sprague-Dawley ; Receptors, Mineralocorticoid/biosynthesis ; Receptors, Mineralocorticoid/genetics ; Reverse Transcriptase Polymerase Chain Reaction
Keywords
diabetic nephropathy ; podocytes ; aldosterone ; apoptosis ; high glucose
Abstract
Previous studies have shown that mineralocorticoid receptor (MCR) blocker reduces proteinuria in diabetic nephropathy (DN), but the role of aldosterone in podocyte injury has never been explored in DN. This study was undertaken to elucidate whether a local aldosterone system existed in podocytes and to examine its role in podocyte apoptosis under diabetic conditions. In vitro, immortalized podocytes were exposed to 5.6 mM glucose (NG), NG + 24.4 mM mannitol, and 30 mM glucose (HG) with or without 10(-7) M spironolactone (SPR). In vivo, 32 Sprague-Dawley rats were injected with diluent (C, n = 16) or streptozotocin intraperitoneally [diabetes mellitus (DM), n = 16], and 8 rats from each group were treated with SPR for 3 mo. Aldosterone synthase (CYP11B2) and MCR mRNA and protein expression were determined by real-time PCR and Western blot, respectively, and aldosterone levels by radioimmunoassay. Western blot for apoptosis-related molecules, Hoechst 33342 staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to determine apoptosis. CYP11B2 and MCR expression were significantly higher in HG-stimulated podocytes and DM glomeruli compared with NG cells and C glomeruli, respectively, along with increased aldosterone levels. Western blot analysis revealed that cleaved caspase-3 and Bax expression was significantly increased, whereas Bcl-2 expression was significantly decreased in HG-stimulated podocytes and in DM glomeruli. Apoptosis determined by Hoechst 33342 staining and TUNEL assay were also significantly increased in podocytes under diabetic conditions. These changes in the expression of apoptosis-related proteins and the increase in apoptotic cells were inhibited by SPR treatment. These findings suggest that a local aldosterone system is activated and is involved in podocyte apoptosis under diabetic conditions.
Files in This Item:
T200903753.pdf Download
DOI
10.1152/ajprenal.00101.2009
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kim, Dong Ki(김동기)
Moon, Sung Jin(문성진)
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Lee, Jung Eun(이정은) ORCID logo https://orcid.org/0000-0003-0917-2872
Han, Dae Suk(한대석)
Han, Seung Jin(한승진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/105353
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