Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions

Sun Ha Lee, Sung Jin Moon, Jisun Paeng, Hye Young Kang, Bo Young Nam, Seonghun Kim, Chan Ho Kim, Mi Jung Lee, Hyung Jung Oh, Jung Tak Park, SeungHyeok Han, TaeHyun Yoo, Shin-Wook Kang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but the sequence in which these processes occur remains a matter of debate. Here we investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa, in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI 166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed significant increases in the protein expression of p27, p21, phospho-eukaryotic elongation factor 4E-binding protein 1, and phospho-p70 S6 ribosomal protein kinase, in both cultured podocytes exposed to high-glucose (HG) medium, and streptozotocin-induced diabetes mellitus (DM) rat glomeruli. These increases were significantly inhibited by PKI 166, but not by zAsp-DCB. In addition, the amount of protein per cell, the relative cell size, and the glomerular volume were all significantly increased under diabetic conditions, and these changes were also blocked by treatment with PKI 166, but not zAsp-DCB. Increased protein expression of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, together with increased Bax/Bcl-2 ratios, were also observed in HG-stimulated podocytes and DM glomeruli. Treatment with either zAsp-DCB or PKI 166 resulted in a significant attenuation of these effects. Both PKI 166 and zAsp-DCB also inhibited the increase in number of apoptotic cells, as assessed by Hoechst 33342 staining and TUNEL assay. Under diabetic conditions, inhibition of podocyte hypertrophy results in attenuated apoptosis, whereas blocking apoptosis has no effect on podocyte hypertrophy, suggesting that podocyte hypertrophy precedes apoptosis.

Original languageEnglish
Pages (from-to)1056-1071
Number of pages16
JournalApoptosis
Volume20
Issue number8
DOIs
Publication statusPublished - 2015 Aug 25

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Podocytes
Hypertrophy
Apoptosis
Medical problems
Diabetes Mellitus
Ribosomal Protein S6 Kinases
Peptide Elongation Factors
Glucose
Proteins
Caspase Inhibitors
Poly(ADP-ribose) Polymerases
Streptozocin
Experimental Diabetes Mellitus
Epidermal Growth Factor Receptor
Caspase 3
In Situ Nick-End Labeling
Rats
Cell Size
Assays
Carrier Proteins

All Science Journal Classification (ASJC) codes

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

Cite this

Lee, S. H., Moon, S. J., Paeng, J., Kang, H. Y., Nam, B. Y., Kim, S., ... Kang, S-W. (2015). Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions. Apoptosis, 20(8), 1056-1071. https://doi.org/10.1007/s10495-015-1134-0
Lee, Sun Ha ; Moon, Sung Jin ; Paeng, Jisun ; Kang, Hye Young ; Nam, Bo Young ; Kim, Seonghun ; Kim, Chan Ho ; Lee, Mi Jung ; Oh, Hyung Jung ; Park, Jung Tak ; Han, SeungHyeok ; Yoo, TaeHyun ; Kang, Shin-Wook. / Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions. In: Apoptosis. 2015 ; Vol. 20, No. 8. pp. 1056-1071.
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Lee, SH, Moon, SJ, Paeng, J, Kang, HY, Nam, BY, Kim, S, Kim, CH, Lee, MJ, Oh, HJ, Park, JT, Han, S, Yoo, T & Kang, S-W 2015, 'Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions', Apoptosis, vol. 20, no. 8, pp. 1056-1071. https://doi.org/10.1007/s10495-015-1134-0

Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions. / Lee, Sun Ha; Moon, Sung Jin; Paeng, Jisun; Kang, Hye Young; Nam, Bo Young; Kim, Seonghun; Kim, Chan Ho; Lee, Mi Jung; Oh, Hyung Jung; Park, Jung Tak; Han, SeungHyeok; Yoo, TaeHyun; Kang, Shin-Wook.

In: Apoptosis, Vol. 20, No. 8, 25.08.2015, p. 1056-1071.

Research output: Contribution to journalArticle

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AU - Lee, Sun Ha

AU - Moon, Sung Jin

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AU - Kim, Chan Ho

AU - Lee, Mi Jung

AU - Oh, Hyung Jung

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AU - Yoo, TaeHyun

AU - Kang, Shin-Wook

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Lee SH, Moon SJ, Paeng J, Kang HY, Nam BY, Kim S et al. Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions. Apoptosis. 2015 Aug 25;20(8):1056-1071. https://doi.org/10.1007/s10495-015-1134-0