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High glucose induces apoptosis of HUVECs in a mitochondria‑dependent manner by suppressing hexokinase 2 expression

  • Authors:
    • Jia Zhang
    • Yanyan Guo
    • Wanyu Ge
    • Xia Zhou
    • Minglin Pan
  • View Affiliations / Copyright

    Affiliations: Sir Run Run Hospital, Nanjing Medical University, Jiangsu, Nanjing 211100, P.R. China, Department of General Medicine, Baota Bridge Community Health Service Center, Jiangsu, Nanjing 210011, P.R. China, Department of Pathology, Anhui Provincial Hospital, Hefei, Anhui 230000, P.R. China, Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Jiangsu, Nanjing 210011, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 621-629
    |
    Published online on: May 24, 2019
       https://doi.org/10.3892/etm.2019.7609
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Abstract

Hyperglycemia in patients with diabetes induces vascular endothelial cell apoptosis and subsequent vasculopathy. The aim of the current study was to investigate the pathological mechanism of hyperglycemia‑induced endothelial cell apoptosis and vasculopathy using human umbilical vein endothelial cells. As high glucose‑induced apoptosis is caused by elevated mitochondrial permeability‑mediated release of mitochondrial cytochrome c, the current study examined voltage‑dependent anion channel (VDAC1), the controller of mitochondrial permeability, and its regulators, hexokinase2 (HK2), Bcl‑2 and Bax. The current study demonstrated that HK2 may be involved in high glucose‑induced cell apoptosis, as HK2 overexpression partially reversed high glucose‑induced downregulation of mitochondrial/cellular HK2 and Bcl‑2 as well as upregulation of mitochondrial Bax. These results suggest that HK2 overexpression partially reversed the reduced binding of HK2 and Bcl‑2 and the enhanced binding of Bax to VDAC1, which reduced the high mitochondrial permeability observed under high‑glucose conditions. Furthermore, high glucose reduced HK2 transcription via down‑regulation of the HK2 transcriptional factor, peroxisome proliferator activated receptor γ (PPARγ). Taken together, these results suggest that PPARγ/HK2 may be novel targets for the prevention of diabetic vasculopathy.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang J, Guo Y, Ge W, Zhou X and Pan M: High glucose induces apoptosis of HUVECs in a mitochondria‑dependent manner by suppressing hexokinase 2 expression. Exp Ther Med 18: 621-629, 2019.
APA
Zhang, J., Guo, Y., Ge, W., Zhou, X., & Pan, M. (2019). High glucose induces apoptosis of HUVECs in a mitochondria‑dependent manner by suppressing hexokinase 2 expression. Experimental and Therapeutic Medicine, 18, 621-629. https://doi.org/10.3892/etm.2019.7609
MLA
Zhang, J., Guo, Y., Ge, W., Zhou, X., Pan, M."High glucose induces apoptosis of HUVECs in a mitochondria‑dependent manner by suppressing hexokinase 2 expression". Experimental and Therapeutic Medicine 18.1 (2019): 621-629.
Chicago
Zhang, J., Guo, Y., Ge, W., Zhou, X., Pan, M."High glucose induces apoptosis of HUVECs in a mitochondria‑dependent manner by suppressing hexokinase 2 expression". Experimental and Therapeutic Medicine 18, no. 1 (2019): 621-629. https://doi.org/10.3892/etm.2019.7609
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang J, Guo Y, Ge W, Zhou X and Pan M: High glucose induces apoptosis of HUVECs in a mitochondria‑dependent manner by suppressing hexokinase 2 expression. Exp Ther Med 18: 621-629, 2019.
APA
Zhang, J., Guo, Y., Ge, W., Zhou, X., & Pan, M. (2019). High glucose induces apoptosis of HUVECs in a mitochondria‑dependent manner by suppressing hexokinase 2 expression. Experimental and Therapeutic Medicine, 18, 621-629. https://doi.org/10.3892/etm.2019.7609
MLA
Zhang, J., Guo, Y., Ge, W., Zhou, X., Pan, M."High glucose induces apoptosis of HUVECs in a mitochondria‑dependent manner by suppressing hexokinase 2 expression". Experimental and Therapeutic Medicine 18.1 (2019): 621-629.
Chicago
Zhang, J., Guo, Y., Ge, W., Zhou, X., Pan, M."High glucose induces apoptosis of HUVECs in a mitochondria‑dependent manner by suppressing hexokinase 2 expression". Experimental and Therapeutic Medicine 18, no. 1 (2019): 621-629. https://doi.org/10.3892/etm.2019.7609
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