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TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway

  • Authors:
    • Meng Wang
    • Wenjian Zhang
    • Shiqing Xu
    • Liang Peng
    • Zai Wang
    • Honglin Liu
    • Qing Fang
    • Tingting Deng
    • Xiuli Men
    • Jinning Lou
  • View Affiliations / Copyright

    Affiliations: Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, P.R. China, Department of Pathophysiology, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 130-136
    |
    Published online on: May 16, 2017
       https://doi.org/10.3892/ijmm.2017.2991
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Abstract

Advanced glycation end products (AGEs), which accumulate in the body during the development of diabetes, may be one of the factors leading to pancreatic β-cell failure and reduced β-cell mass. However, the mechanisms responsible for AGE‑induced apoptosis remain unclear. This study identified the role and mechanisms of action of tribbles homolog 3 (TRB3) in AGE-induced β-cell oxidative damage and apoptosis. Rat insulinoma cells (INS-1) were treated with 200 µg/ml AGEs for 48 h, and cell apoptosis was then detected by TUNEL staining and flow cytometry. The level of intracellular reactive oxygen species (ROS) was measured by a fluorescence assay. The expression levels of receptor of AGEs (RAGE), TRB3, protein kinase C β2 (PKCβ2) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) were evaluated by RT-qPCR and western blot analysis. siRNA was used to knockdown TRB3 expression through lipofection, followed by an analysis of the effects of TRB3 on PKCβ2 and NOX4. Furthermore, the PKCβ2-specific inhibitor, LY333531, was used to analyze the effects of PKCβ2 on ROS levels and apoptosis. We found that AGEs induced the apoptosis of INS-1 cells and upregulated RAGE and TRB3 expression. AGEs also increased ROS levels in β-cells. Following the knockdown of TRB3, the AGE-induced apoptosis and intracellular ROS levels were significantly decreased, suggesting that TRB3 mediated AGE-induced apoptosis. Further experiments demonstrated that the knockdown of TRB3 decreased the PKCβ2 and NOX4 expression levels. When TRB3 was knocked down, the cells expressed decreased levels of PKCβ2 and NOX4. The PKCβ2‑specific inhibitor, LY333531, also reduced AGE-induced apoptosis and intracellular ROS levels. Taken together, our data suggest that TRB3 mediates AGE-induced oxidative injury in β-cells through the PKCβ2 pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Wang M, Zhang W, Xu S, Peng L, Wang Z, Liu H, Fang Q, Deng T, Men X, Lou J, Lou J, et al: TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway. Int J Mol Med 40: 130-136, 2017.
APA
Wang, M., Zhang, W., Xu, S., Peng, L., Wang, Z., Liu, H. ... Lou, J. (2017). TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway. International Journal of Molecular Medicine, 40, 130-136. https://doi.org/10.3892/ijmm.2017.2991
MLA
Wang, M., Zhang, W., Xu, S., Peng, L., Wang, Z., Liu, H., Fang, Q., Deng, T., Men, X., Lou, J."TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway". International Journal of Molecular Medicine 40.1 (2017): 130-136.
Chicago
Wang, M., Zhang, W., Xu, S., Peng, L., Wang, Z., Liu, H., Fang, Q., Deng, T., Men, X., Lou, J."TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway". International Journal of Molecular Medicine 40, no. 1 (2017): 130-136. https://doi.org/10.3892/ijmm.2017.2991
Copy and paste a formatted citation
x
Spandidos Publications style
Wang M, Zhang W, Xu S, Peng L, Wang Z, Liu H, Fang Q, Deng T, Men X, Lou J, Lou J, et al: TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway. Int J Mol Med 40: 130-136, 2017.
APA
Wang, M., Zhang, W., Xu, S., Peng, L., Wang, Z., Liu, H. ... Lou, J. (2017). TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway. International Journal of Molecular Medicine, 40, 130-136. https://doi.org/10.3892/ijmm.2017.2991
MLA
Wang, M., Zhang, W., Xu, S., Peng, L., Wang, Z., Liu, H., Fang, Q., Deng, T., Men, X., Lou, J."TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway". International Journal of Molecular Medicine 40.1 (2017): 130-136.
Chicago
Wang, M., Zhang, W., Xu, S., Peng, L., Wang, Z., Liu, H., Fang, Q., Deng, T., Men, X., Lou, J."TRB3 mediates advanced glycation end product-induced apoptosis of pancreatic β-cells through the protein kinase C β pathway". International Journal of Molecular Medicine 40, no. 1 (2017): 130-136. https://doi.org/10.3892/ijmm.2017.2991
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