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International Journal of Molecular Medicine
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2014-April Volume 33 Issue 4

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Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose

  • Authors:
    • Yanping Cao
    • Yongmei Hao
    • Hang Li
    • Qingjuan Liu
    • Feng Gao
    • Wei Liu
    • Huijun Duan
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei 05001, P.R. China, Department of Pathology, The Third Hospital, Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
    Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 809-816
    |
    Published online on: February 3, 2014
       https://doi.org/10.3892/ijmm.2014.1642
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Abstract

Podocytes are terminally differentiated epithelial cells lacking the ability to proliferate. The loss of podocytes is a hallmark of progressive kidney diseases, including diabetic nephropathy (DN). Endoplasmic reticulum stress (ERS)-induced apoptosis is involved in a number of pathological conditions, including DN. The aim of the present study was to investigate whether a high glucose environment induces the apoptosis of podocytes through ERS. Differentiated mouse podocytes were divided into three groups: the normal glucose group (NG, 1 g/l D-glucose), the high glucose group (HG, 4.5 g/l D-glucose) and the mannitol group (M, 1 g/l D-glucose plus 24.4 mM mannitol). The cells were harvested following stimulation with the indicated treatments for 12, 24, 48 and 72 h. Podocyte apoptosis was determined using TUNEL assay and flow cytometry (propidium iodide staining). Glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP/GADD153) and caspase-12 expression was analyzed by RT-PCR, western blot analysis and immunocytochemistry. The apoptotic rate increased significantly in the HG group compared with the NG and M groups at 48 and 72 h (all P<0.01). GRP78 expression, an indicator of ERS, was increased from 12 h, indicating that ERS was activated. Subsequently, two ER-associated death (ERAD) pathways, the CHOP/GADD153- and caspase‑12-dependent pathways, were detected. CHOP/GADD153 expression reached its peak at 48 h, and caspase-12 expression gradually increased with time. Spearman's correlation analysis revealed that caspase-12 and CHOP/GADD153 positively correlated with the apoptotic rate (r=0.915, P<0.01 and r=0.639, P<0.01). Our results demonstrated that hyperglycemia (high glucose) induced apoptosis partly through ERS in the differentiated mouse podocytes, which possibly contributes to the pathogenesis of DN.
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1 

Pavkov ME, Knowler WC, Bennett PH, Looker HC, Krakoff J and Nelson RG: Increasing incidence of proteinuria and declining incidence of end-stage renal disease in diabetic Pima Indians. Kidney Int. 70:1840–1846. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Cowie CC, Port FK, Wolfe RA, Savage PJ, Moll PP and Hawthorne VM: Disparities in incidence of diabetic end-stage renal disease according to race and type of diabetes. N Engl J Med. 321:1074–1079. 1989. View Article : Google Scholar : PubMed/NCBI

3 

Adler S: Diabetic nephropathy: linking histology, cell biology, and genetics. Kidney Int. 66:2095–2106. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Mason RM and Wahab NA: Extracellular matrix metabolism in diabetic nephropathy. J Am Soc Nephrol. 14:1358–1373. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Shankland SJ: The podocyte’s response to injury: role in proteinuria and glomerulosclerosis. Kidney Int. 69:2131–2147. 2006.

6 

Mundel P and Shankland SJ: Podocyte biology and response to injury. J Am Soc Nephrol. 13:3005–3015. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Kriz W, Gretz N and Lemley KV: Progression of glomerular diseases: is the podocyte the culprit? Kidney Int. 54:687–697. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Xu C, Bailly-Maitre B and Reed JC: Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest. 115:2656–2664. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Marciniak SJ, Yun CY, Oyadomari S, et al: CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 18:3066–3077. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Susztak K, Raff AC, Schiffer M and Böttinger EP: Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes. 55:225–233. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Siu B, Saha J, Smoyer WE, Sullivan KA and Brosius FC III: Reduction in podocyte density as a pathologic feature in early diabetic nephropathy in rodents: prevention by lipoic acid treatment. BMC Nephrol. 7:62006. View Article : Google Scholar : PubMed/NCBI

12 

King GL and Loeken MR: Hyperglycemia-induced oxidative stress in diabetic complications. Histochem Cell Biol. 122:333–338. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Zhang W, Feng D, Li Y, Iida K, McGrath B and Cavener DR: PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis. Cell Metab. 4:491–497. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Laybutt DR, Preston AM, Akerfeldt MC, et al: Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. Diabetologia. 50:752–763. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Ron D and Walter P: Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 8:519–529. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Rao RV, Peel A, Logvinova A, et al: Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett. 514:122–128. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Zinszner H, Kuroda M, Wang X, et al: CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 12:982–995. 1998. View Article : Google Scholar : PubMed/NCBI

18 

Szegezdi E, Logue SE, Gorman AM and Samali A: Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep. 7:880–885. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Butt A and Riaz S: Study of protein profiling of human urine in diabetic hypertensive nephropathy versus normal healthy controls. Diabetes Technol Ther. 12:379–386. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Chen M, Felix K and Wang J: Immune regulation through mitochondrion-dependent dendritic cell death induced by T regulatory cells. J Immunol. 187:5684–5692. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Liu G, Sun Y, Li Z, et al: Apoptosis induced by endoplasmic reticulum stress involved in diabetic kidney disease. Biochem Biophys Res Commun. 370:651–656. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Ron D and Habener JF: CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 6:439–453. 1992. View Article : Google Scholar

23 

Wang XZ, Lawson B, Brewer JW, et al: Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Mol Cell Biol. 16:4273–4280. 1996.PubMed/NCBI

24 

Matsumoto M, Minami M, Takeda K, Sakao Y and Akira S: Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells. FEBS Lett. 395:143–147. 1996. View Article : Google Scholar : PubMed/NCBI

25 

Maytin EV, Ubeda M, Lin JC and Habener JF: Stress-inducible transcription factor CHOP/gadd153 induces apoptosis in mammalian cells via p38 kinase-dependent and -independent mechanisms. Exp Cell Res. 267:193–204. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Oyadomari S, Takeda K, Takiguchi M, et al: Nitric oxide-induced apoptosis in pancreatic beta cells is mediated by the endoplasmic reticulum stress pathway. Proc Natl Acad Sci USA. 98:10845–10850. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Gotoh T, Oyadomari S, Mori K and Mori M: Nitric oxide-induced apoptosis in RAW 264.7 macrophages is mediated by endoplasmic reticulum stress pathway involving ATF6 and CHOP. J Biol Chem. 277:12343–12350. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Oyadomari S and Mori M: Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 11:381–389. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Nakagawa T and Yuan J: Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol. 150:887–894. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Liu H and Baliga R: Endoplasmic reticulum stress-associated caspase 12 mediates cisplatin-induced LLC-PK1 cell apoptosis. J Am Soc Nephrol. 16:1985–1992. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Cao Y, Hao Y, Li H, Liu Q, Gao F, Liu W and Duan H: Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose. Int J Mol Med 33: 809-816, 2014.
APA
Cao, Y., Hao, Y., Li, H., Liu, Q., Gao, F., Liu, W., & Duan, H. (2014). Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose. International Journal of Molecular Medicine, 33, 809-816. https://doi.org/10.3892/ijmm.2014.1642
MLA
Cao, Y., Hao, Y., Li, H., Liu, Q., Gao, F., Liu, W., Duan, H."Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose". International Journal of Molecular Medicine 33.4 (2014): 809-816.
Chicago
Cao, Y., Hao, Y., Li, H., Liu, Q., Gao, F., Liu, W., Duan, H."Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose". International Journal of Molecular Medicine 33, no. 4 (2014): 809-816. https://doi.org/10.3892/ijmm.2014.1642
Copy and paste a formatted citation
x
Spandidos Publications style
Cao Y, Hao Y, Li H, Liu Q, Gao F, Liu W and Duan H: Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose. Int J Mol Med 33: 809-816, 2014.
APA
Cao, Y., Hao, Y., Li, H., Liu, Q., Gao, F., Liu, W., & Duan, H. (2014). Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose. International Journal of Molecular Medicine, 33, 809-816. https://doi.org/10.3892/ijmm.2014.1642
MLA
Cao, Y., Hao, Y., Li, H., Liu, Q., Gao, F., Liu, W., Duan, H."Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose". International Journal of Molecular Medicine 33.4 (2014): 809-816.
Chicago
Cao, Y., Hao, Y., Li, H., Liu, Q., Gao, F., Liu, W., Duan, H."Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose". International Journal of Molecular Medicine 33, no. 4 (2014): 809-816. https://doi.org/10.3892/ijmm.2014.1642
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