Radioprotective 105 kDa protein attenuates ischemia/reperfusion-induced myocardial apoptosis and autophagy by inhibiting the activation of the TLR4/NF-κB signaling pathway in rats

  • Authors:
    • Xin Guo
    • Hong Jiang
    • Jun Yang
    • Jing Chen
    • Jian Yang
    • Jia-Wang Ding
    • Song Li
    • Hui Wu
    • Hua-Sheng Ding
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  • Published online on: July 19, 2016     https://doi.org/10.3892/ijmm.2016.2686
  • Pages: 885-893
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Abstract

Toll-like receptor 4 (TLR4) serves as an important inducer of apoptotic and autophagic responses in myocardial ischemia/reperfusion (I/R) injury (MIRI). Radioprotective 105 kDa protein (RP105) is a specific inhibitor of TLR4. However, the molecular mechanisms by which RP105 represses myocardial apoptosis and autophagy through TLR4‑mediated signaling during I/R have not yet been fully elucidated. Therefore, in the present study, we aimed to examine whether adenovirus-mediated RP105 overexpression repressed myocardial apoptosis and autophagy by inhibiting the TLR4-driven mechanism in MIRI. Three days after the injection of virus or saline into the myocardium, Sprague-Dawley (SD) rats were subjected to 30 min of left anterior descending coronary artery occlusion and 6 h of reperfusion. Myocardial specimens were prepared for analysis. We performed immunohistochemichal and histopathological analysis, the measurement of cardiac biomarkers, TUNEL assay , RT-qPCR and western blot analysis. The results indicated that the overexpression of RP105 contributed to an amelioration of myocardial histological damage, decreased leakage of creatine kinase (CK) and lactate dehydrogenase (LDH), as well as a reduction in the number of TUNEL-positive cardiomyocytes. The levels of positively associated modulators of apoptosis and autophagy were also significantly downregulated by RP105, whereas Bcl-2, which plays an opposite role in inducing apoptosis and autophagy, was inversely upregulated. Furthermore, the overexpression of RP105 led to the repression of TLR4 activity and the phosphorylation of NF-κB/p65, as well as the reduced production of the cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). Taken together, these data suggest that RP105 protects the myocardium against apoptosis and autophagy, and plays a cardioprotective role during I/R injury. This is most likely due to the inactivation of TLR4/NF-κB signaling pathway. Thus, RP105 may represent an innovative therapeutic target for attenuating MIRI.
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September-2016
Volume 38 Issue 3

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

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Spandidos Publications style
Guo X, Jiang H, Yang J, Chen J, Yang J, Ding J, Li S, Wu H and Ding H: Radioprotective 105 kDa protein attenuates ischemia/reperfusion-induced myocardial apoptosis and autophagy by inhibiting the activation of the TLR4/NF-κB signaling pathway in rats. Int J Mol Med 38: 885-893, 2016.
APA
Guo, X., Jiang, H., Yang, J., Chen, J., Yang, J., Ding, J. ... Ding, H. (2016). Radioprotective 105 kDa protein attenuates ischemia/reperfusion-induced myocardial apoptosis and autophagy by inhibiting the activation of the TLR4/NF-κB signaling pathway in rats. International Journal of Molecular Medicine, 38, 885-893. https://doi.org/10.3892/ijmm.2016.2686
MLA
Guo, X., Jiang, H., Yang, J., Chen, J., Yang, J., Ding, J., Li, S., Wu, H., Ding, H."Radioprotective 105 kDa protein attenuates ischemia/reperfusion-induced myocardial apoptosis and autophagy by inhibiting the activation of the TLR4/NF-κB signaling pathway in rats". International Journal of Molecular Medicine 38.3 (2016): 885-893.
Chicago
Guo, X., Jiang, H., Yang, J., Chen, J., Yang, J., Ding, J., Li, S., Wu, H., Ding, H."Radioprotective 105 kDa protein attenuates ischemia/reperfusion-induced myocardial apoptosis and autophagy by inhibiting the activation of the TLR4/NF-κB signaling pathway in rats". International Journal of Molecular Medicine 38, no. 3 (2016): 885-893. https://doi.org/10.3892/ijmm.2016.2686