title: Apoptosis occurs differentially according to glomerular size in diabetic kidney disease.
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.
authors.affiliation: Department of Internal Medicine, College of Medicine, Brain Korea 21, Severance Biomedical Science Institute, Yonsei University, Seoul, Korea.
authors.forename: Dong-Sub
authors.initials: DS
authors.lastname: Jung
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Lee
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Kwak
authors.forename: Jin Ji
authors.initials: JJ
authors.lastname: Li
authors.forename: Do Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Nam
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kang
authors.forename: Tae Ik
authors.initials: TI
authors.lastname: Chang
authors.forename: Jung Tak
authors.initials: JT
authors.lastname: Park
authors.forename: Seung Hyeok
authors.initials: SH
authors.lastname: Han
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Yoo
authors.forename: Shin-Wook
authors.initials: SW
authors.lastname: Kang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010766:Phosphorylation; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3