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Apoptosis occurs differentially according to glomerular size in diabetic kidney disease

Authors
 Dong-Sub Jung  ;  Sun Ha Lee  ;  Seung-Jae Kwak  ;  Jin Ji Li  ;  Do Hee Kim  ;  Bo-Young Nam  ;  Hye Young Kang  ;  Tae Ik Chang  ;  Jung Tak Park  ;  Seung Hyeok Han  ;  Tae-Hyun Yoo  ;  Shin-Wook Kang 
Citation
 NEPHROLOGY DIALYSIS TRANSPLANTATION, Vol.27(1) : 259-266, 2012 
Journal Title
 NEPHROLOGY DIALYSIS TRANSPLANTATION 
ISSN
 0931-0509 
Issue Date
2012
MeSH
Animals ; Apoptosis* ; Blotting, Western ; Caspase 3/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology* ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/pathology* ; Fluorescent Antibody Technique ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology* ; Male ; Phosphorylation ; Podocytes/metabolism ; Podocytes/pathology* ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein/metabolism
Keywords
Animals ; Apoptosis* ; Blotting, Western ; Caspase 3/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology* ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/pathology* ; Fluorescent Antibody Technique ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology* ; Male ; Phosphorylation ; Podocytes/metabolism ; Podocytes/pathology* ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein/metabolism
Abstract
BACKGROUND: Apoptosis; which is involved in the process of mesangial cell and podocyte loss in diabetic nephropathy; is known to be regulated by protein kinase B/Akt (Akt). A number of studies have therefore investigated the activity of Akt under diabetic conditions; but the results have not been consistent. In this study; we hypothesized that apoptosis may occur differentially and that Akt may be differentially activated according to glomerular size in diabetic kidney disease. METHODS: Fifty male Sprague-Dawley rats were injected intraperitoneally with diluent (C; n = 25) or streptozotocin (DM; n = 25). After 3 months; glomeruli were isolated using sieves with pore sizes of 250; 150; 125 and 75 μm and then classified into large glomeruli (on the 125-μm sieve; LG) and small glomeruli (on the 75-μm sieve; SG) groups. Western blot analyses for phospho-Akt; apoptosis-related molecules (Bax; Bcl-2; active fragments of Caspase-3 and phospho-p53) and cyclin-dependent kinase inhibitors were performed. CONCLUSIONS: The numbers of total cells and podocytes in isolated glomeruli were determined using transmission electron microscopy. Akt phosphorylation was significantly decreased in DM-LG; while it was significantly increased in DM-SG (P < 0.05). The ratio of Bax/Bcl-2 protein expression and active fragments of Caspase-3 and phospho-p53 protein expression were significantly increased in DM-LG compared to DM-SG and C-SG (P < 0.001 and P < 0.01; respectively). In contrast; the expression of p27(Kip1) and p21(Cip1) was significantly increased in DM-SG compared to DM-LG and C-SG (P < 0.05). The numbers of total glomerular cells and podocytes were significantly decreased in DM-LG (P < 0.05). In conclusion; these data show differential expression of Akt activity and apoptosis-related molecules according to glomerular size in diabetic nephropathy; suggesting that apoptosis may be more operative in more hypertrophic glomeruli; resulting in fewer glomerular cells and podocytes in diabetic nephropathy.
Full Text
http://ndt.oxfordjournals.org/content/27/1/259.long
DOI
21652547
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kang, Hye Young(강혜영)
Kwak, Seung Jae(곽승재)
Nam, Bo Young(남보영)
Park, Jung Tak(박정탁) ORCID logo https://orcid.org/0000-0002-2325-8982
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Lee, Sun Ha(이순하)
Chang, Tae Ik(장태익)
Jung, Dong Sub(정동섭)
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91514
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