PMID- 19710242
OWN - NLM
STAT- MEDLINE
DCOM- 20091117
LR  - 20161125
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 297
IP  - 5
DP  - 2009 Nov
TI  - Activation of local aldosterone system within podocytes is involved in apoptosis 
      under diabetic conditions.
PG  - F1381-90
LID - 10.1152/ajprenal.00101.2009 [doi]
AB  - 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.
FAU - Lee, Sun Ha
AU  - Lee SH
AD  - Department of Internal Medicine, College of Medicine, Brain Korea 21 for Medical 
      Science, Yonsei University, Seoul, Korea.
FAU - Yoo, Tae-Hyun
AU  - Yoo TH
FAU - Nam, Bo-Young
AU  - Nam BY
FAU - Kim, Dong Ki
AU  - Kim DK
FAU - Li, Jin Ji
AU  - Li JJ
FAU - Jung, Dong-Sub
AU  - Jung DS
FAU - Kwak, Seung-Jae
AU  - Kwak SJ
FAU - Ryu, Dong-Ryeol
AU  - Ryu DR
FAU - Han, Seung Hyeok
AU  - Han SH
FAU - Lee, Jung Eun
AU  - Lee JE
FAU - Moon, Sung Jin
AU  - Moon SJ
FAU - Han, Dae Suk
AU  - Han DS
FAU - Kang, Shin-Wook
AU  - Kang SW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090826
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Benzimidazoles)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - 4964P6T9RB (Aldosterone)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2)
RN  - EC 1.14.15.4 (Cytochrome P-450 CYP11B2)
RN  - EC 3.4.22.- (Caspase 3)
RN  - P976261J69 (bisbenzimide ethoxide trihydrochloride)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenase Type 2/biosynthesis/genetics
MH  - Aldosterone/*physiology
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Apoptosis Regulatory Proteins/biosynthesis/genetics
MH  - Benzimidazoles
MH  - Blotting, Western
MH  - Caspase 3/biosynthesis/genetics
MH  - Cell Count
MH  - Cells, Cultured
MH  - Cytochrome P-450 CYP11B2/biosynthesis/genetics
MH  - Diabetes Mellitus, Experimental/*pathology
MH  - Fluorescent Antibody Technique
MH  - Fluorescent Dyes
MH  - In Situ Nick-End Labeling
MH  - Kidney/pathology
MH  - Kidney Glomerulus/metabolism
MH  - Male
MH  - Podocytes/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Mineralocorticoid/biosynthesis/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2009/08/28 09:00
MHDA- 2009/11/18 06:00
CRDT- 2009/08/28 09:00
PHST- 2009/08/28 09:00 [entrez]
PHST- 2009/08/28 09:00 [pubmed]
PHST- 2009/11/18 06:00 [medline]
AID - 00101.2009 [pii]
AID - 10.1152/ajprenal.00101.2009 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2009 Nov;297(5):F1381-90. doi: 
      10.1152/ajprenal.00101.2009. Epub 2009 Aug 26.