Enhanced glycogen synthase kinase-3β activity mediates podocyte apoptosis under diabetic conditions

Jisun Paeng, Jae Hyun Chang, Sun Ha Lee, Bo Young Nam, Hye Young Kang, Seonghun Kim, Hyung Jung Oh, Jung Tak Park, SeungHyeok Han, TaeHyun Yoo, Shin-Wook Kang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Glycogen synthase kinase-3β (GSK-3β) is involved in the pathogenesis of various kidney diseases. This study was undertaken to examine the changes in GSK-3β activity in podocytes under diabetic conditions and to elucidate the functional role of GSK-3β in podocyte apoptosis. In vivo, 32 rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with 6-bromoindirubin-3′-oxime (BIO) for 3 months. In vitro, immortalized mouse podocytes were exposed to 5.6 mM glucose or 30 mM glucose (HG) with or without 10 μM BIO. Western blot analysis and TUNEL or Hoechst 33342 staining were performed to identify apoptosis. Urinary albumin excretion was significantly higher in DM rats, and this increase was significantly abrogated in DM rats by BIO treatment. The protein expression of Tyr216-phospho-GSK-3β was significantly increased in DM glomeruli and in cultured podocytes exposed to HG. Western blot analysis revealed that the protein expression of Bax and active fragments of caspase-3 were significantly increased, whereas phospho-Akt, β-catenin, and Bcl-2 protein expression were significantly decreased in DM glomeruli and HG-stimulated podocytes. Apoptosis, determined by TUNEL assay and Hoechst 33342 staining, was also significantly increased in podocytes under diabetic conditions. The changes in the expression of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG-stimulated podocytes were significantly ameliorated by BIO. These findings suggest that enhanced GSK-3β activity within podocytes under diabetic conditions is associated with podocyte loss in diabetic nephropathy.

Original languageEnglish
Pages (from-to)1678-1690
Number of pages13
JournalApoptosis
Volume19
Issue number12
DOIs
Publication statusPublished - 2014 Nov 8

Fingerprint

Glycogen Synthase Kinase 3
Podocytes
Oximes
Apoptosis
Rats
Glucose
Catenins
In Situ Nick-End Labeling
Proteins
Streptozocin
Caspase 3
Albumins
Assays
Western Blotting
Staining and Labeling
Cells
bcl-2-Associated X Protein
Kidney Diseases
Molecules
Diabetic Nephropathies

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Cite this

Paeng, Jisun ; Chang, Jae Hyun ; Lee, Sun Ha ; Nam, Bo Young ; Kang, Hye Young ; Kim, Seonghun ; Oh, Hyung Jung ; Park, Jung Tak ; Han, SeungHyeok ; Yoo, TaeHyun ; Kang, Shin-Wook. / Enhanced glycogen synthase kinase-3β activity mediates podocyte apoptosis under diabetic conditions. In: Apoptosis. 2014 ; Vol. 19, No. 12. pp. 1678-1690.
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abstract = "Glycogen synthase kinase-3β (GSK-3β) is involved in the pathogenesis of various kidney diseases. This study was undertaken to examine the changes in GSK-3β activity in podocytes under diabetic conditions and to elucidate the functional role of GSK-3β in podocyte apoptosis. In vivo, 32 rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with 6-bromoindirubin-3′-oxime (BIO) for 3 months. In vitro, immortalized mouse podocytes were exposed to 5.6 mM glucose or 30 mM glucose (HG) with or without 10 μM BIO. Western blot analysis and TUNEL or Hoechst 33342 staining were performed to identify apoptosis. Urinary albumin excretion was significantly higher in DM rats, and this increase was significantly abrogated in DM rats by BIO treatment. The protein expression of Tyr216-phospho-GSK-3β was significantly increased in DM glomeruli and in cultured podocytes exposed to HG. Western blot analysis revealed that the protein expression of Bax and active fragments of caspase-3 were significantly increased, whereas phospho-Akt, β-catenin, and Bcl-2 protein expression were significantly decreased in DM glomeruli and HG-stimulated podocytes. Apoptosis, determined by TUNEL assay and Hoechst 33342 staining, was also significantly increased in podocytes under diabetic conditions. The changes in the expression of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG-stimulated podocytes were significantly ameliorated by BIO. These findings suggest that enhanced GSK-3β activity within podocytes under diabetic conditions is associated with podocyte loss in diabetic nephropathy.",
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Enhanced glycogen synthase kinase-3β activity mediates podocyte apoptosis under diabetic conditions. / Paeng, Jisun; Chang, Jae Hyun; Lee, Sun Ha; Nam, Bo Young; Kang, Hye Young; Kim, Seonghun; Oh, Hyung Jung; Park, Jung Tak; Han, SeungHyeok; Yoo, TaeHyun; Kang, Shin-Wook.

In: Apoptosis, Vol. 19, No. 12, 08.11.2014, p. 1678-1690.

Research output: Contribution to journalArticle

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AU - Paeng, Jisun

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AU - Kim, Seonghun

AU - Oh, Hyung Jung

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AU - Kang, Shin-Wook

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