Potential role of ATM in hepatocyte endocytosis of ApoE-deficient, ApoB48-containing lipoprotein in ApoE-deficient mice

  • Authors:
    • Jianhua Wu
    • Yanhong Xiao
    • Juang Liu
    • Hong Yang
    • Xiaomin Dong
    • San Hu
    • Shanrui Jin
    • Dongfang Wu
  • View Affiliations

  • Published online on: November 26, 2013     https://doi.org/10.3892/ijmm.2013.1566
  • Pages: 462-468
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Abstract

Individuals carrying mutations at both ataxia telangiectasia mutated (ATM) gene alleles reportedly have increased plasma cholesterol and triglyceride levels. Previous studies have demonstrated that defective ATM function promotes atherosclerosis. We previously demonstrated that ATM facilitates the clearance of plasma apolipoprotein (Apo)E-deficient, ApoB48-containing (E-/B48) lipoproteins in ApoE-deficient mice (ApoE-/- mice). However, to date there is no exact explanation available as to the mechanism(s) through which ATM is involved in the removal of E-/B48 lipoprotein in ApoE-/- mice. In this study, to our knowledge, we demonstrate for the first time that heterozygous ATM mutation reduces the hepatocyte uptake of E-/B48 lipoproteins in ApoE-/- mice; however, heterozygous ATM mutation did not affect hepatocyte binding to E-/B48 lipoproteins. Moreover, our results revealed that ATM proteins were localized in the nucleus, early endosomes and late endosomes, but not in the plasma membrane in the hepatocytes of ApoE-/- mice. In addition, following treatment with the ATM activator, chloroquine, and E-/B48 lipoproteins, ATM interacted with class III phosphatidylinositol-3-kinases (PI3Ks) and the activated ATM protein enhanced class III PI3K activity. Furthermore, treatment with a class III PI3K inhibitor (LY290042 and 3-MA) attenuated the intracellular total cholesterol accumulation induced by ATM activation. These results provide insight into the mechanisms behind the involvment of ATM in the process of endocytosis of E-/B48 lipoprotein in ApoE-/- mice, demonstrating the role of class III PI3K protein.
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2014-February
Volume 33 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Wu J, Xiao Y, Liu J, Yang H, Dong X, Hu S, Jin S and Wu D: Potential role of ATM in hepatocyte endocytosis of ApoE-deficient, ApoB48-containing lipoprotein in ApoE-deficient mice . Int J Mol Med 33: 462-468, 2014
APA
Wu, J., Xiao, Y., Liu, J., Yang, H., Dong, X., Hu, S. ... Wu, D. (2014). Potential role of ATM in hepatocyte endocytosis of ApoE-deficient, ApoB48-containing lipoprotein in ApoE-deficient mice . International Journal of Molecular Medicine, 33, 462-468. https://doi.org/10.3892/ijmm.2013.1566
MLA
Wu, J., Xiao, Y., Liu, J., Yang, H., Dong, X., Hu, S., Jin, S., Wu, D."Potential role of ATM in hepatocyte endocytosis of ApoE-deficient, ApoB48-containing lipoprotein in ApoE-deficient mice ". International Journal of Molecular Medicine 33.2 (2014): 462-468.
Chicago
Wu, J., Xiao, Y., Liu, J., Yang, H., Dong, X., Hu, S., Jin, S., Wu, D."Potential role of ATM in hepatocyte endocytosis of ApoE-deficient, ApoB48-containing lipoprotein in ApoE-deficient mice ". International Journal of Molecular Medicine 33, no. 2 (2014): 462-468. https://doi.org/10.3892/ijmm.2013.1566