Apoptosis occurs differentially according to glomerular size in diabetic kidney disease

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, SeungHyeok Han, TaeHyun Yoo, Shin-Wook Kang

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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.

Original languageEnglish
Pages (from-to)259-266
Number of pages8
JournalNephrology Dialysis Transplantation
Volume27
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1

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Diabetic Nephropathies
Podocytes
Apoptosis
Caspase 3
Proto-Oncogene Proteins c-akt
Mesangial Cells
Cyclin-Dependent Kinases
Streptozocin
Transmission Electron Microscopy
Sprague Dawley Rats
Proteins
Cell Count
Western Blotting
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

Cite this

Jung, Dong Sub ; Lee, Sun Ha ; Kwak, Seung Jae ; Li, Jin Ji ; Kim, Do Hee ; Nam, Bo Young ; Kang, Hye Young ; Chang, Tae Ik ; Park, Jung Tak ; Han, SeungHyeok ; Yoo, TaeHyun ; Kang, Shin-Wook. / Apoptosis occurs differentially according to glomerular size in diabetic kidney disease. In: Nephrology Dialysis Transplantation. 2012 ; Vol. 27, No. 1. pp. 259-266.
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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.",
author = "Jung, {Dong Sub} and Lee, {Sun Ha} and Kwak, {Seung Jae} and Li, {Jin Ji} and Kim, {Do Hee} and Nam, {Bo Young} and Kang, {Hye Young} and Chang, {Tae Ik} and Park, {Jung Tak} and SeungHyeok Han and TaeHyun Yoo and Shin-Wook Kang",
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Jung, DS, Lee, SH, Kwak, SJ, Li, JJ, Kim, DH, Nam, BY, Kang, HY, Chang, TI, Park, JT, Han, S, Yoo, T & Kang, S-W 2012, 'Apoptosis occurs differentially according to glomerular size in diabetic kidney disease', Nephrology Dialysis Transplantation, vol. 27, no. 1, pp. 259-266. https://doi.org/10.1093/ndt/gfr301

Apoptosis occurs differentially according to glomerular size in diabetic kidney disease. / Jung, Dong Sub; Lee, Sun Ha; Kwak, Seung Jae; Li, Jin Ji; Kim, Do Hee; Nam, Bo Young; Kang, Hye Young; Chang, Tae Ik; Park, Jung Tak; Han, SeungHyeok; Yoo, TaeHyun; Kang, Shin-Wook.

In: Nephrology Dialysis Transplantation, Vol. 27, No. 1, 01.01.2012, p. 259-266.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apoptosis occurs differentially according to glomerular size in diabetic kidney disease

AU - Jung, Dong Sub

AU - Lee, Sun Ha

AU - Kwak, Seung Jae

AU - Li, Jin Ji

AU - Kim, Do Hee

AU - Nam, Bo Young

AU - Kang, Hye Young

AU - Chang, Tae Ik

AU - Park, Jung Tak

AU - Han, SeungHyeok

AU - Yoo, TaeHyun

AU - Kang, Shin-Wook

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

AB - 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.

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