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International Journal of Molecular Medicine
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Inhibition of serine/threonine protein phosphatase PP1 protects cardiomyocytes from tunicamycin‑induced apoptosis and I/R through the upregulation of p-eIF2α

  • Authors:
    • Chun-Lei Liu
    • Yun-Yun He
    • Xin Li
    • Rui-Jun Li
    • Kun-Lun He
    • Li-Li Wang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, P.R. China, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 499-506
    |
    Published online on: December 23, 2013
       https://doi.org/10.3892/ijmm.2013.1603
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Abstract

The serine/threonine protein phosphatase PP1 mediates the dephosphorylation of phosphorylated eukaryotic translation initiation factor 2 subunit α (p-eIF2α), which is a central regulator of protein synthesis. In the present study, we examined the protective effects of PP1-12 (an inhibitor of the serine/threonine protein phosphatase PP1) against tunicamycin (TM)-induced apoptosis in cultured cardiomyocytes in vitro, as well as in an in vivo model of ischemia/reperfusion (I/R) injury in rat hearts. Neonatal cardiomyocytes cultured from the ventricles of the hearts of 1-day-old Wistar rats were exposed to various concentrations of PP1-12 (0.3, 1 and 3 µmol/l) for 30 min, followed by treatment with TM for 36 h. Cell viability was assessed by adenosine triphosphate (ATP) bioluminescence, and the results revealed that pre-treatment with PP1-12 protected cell viability. Western blot analysis revealed that PP1-12 induced eIF2α phosphorylation and immuncytochemistry indicated that PP1-12 downregulated the expression of C/EBP homologous protein (CHOP), which is related to apoptosis. PP1-12 suppressed cell apoptosis, with maximum protective effects displayed at the concentration of 3 µmol/l. For the in vivo experiments, male Sprague-Dawley rats were randomly divided into 5 groups: ⅰ) sham-operated; ⅱ) vehicle (I/R + DMSO); ⅲ) I/R + 1 mg/kg/day PP1-12; ⅳ) I/R + 3 mg/kg/day PP1-12; and ⅴ) I/R + 10 mg/kg/day PP1-12. PP1-12 reduced the expression of cleaved caspase‑12 and increased the phosphorylation of eIF2α, as revealed by western blot analysis. By calculating the apoptotic index (AI), we found that 10 mg/kg/day PP1-12 exerted the most pronounced anti-apoptotic effect. The infarction area was significantly decreased following treatment with this concentration of PP1-12, as revealed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Taken together, these data suggest that PP1-12 protects cardiomyocytes from TM- and I/R-induced apoptosis, and this effect is achieved at least in part through the inhibition of cell apoptosis and the induction of eIF2α phosphorylation.
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Copy and paste a formatted citation
Spandidos Publications style
Liu C, He Y, Li X, Li R, He K and Wang L: Inhibition of serine/threonine protein phosphatase PP1 protects cardiomyocytes from tunicamycin‑induced apoptosis and I/R through the upregulation of p-eIF2α. Int J Mol Med 33: 499-506, 2014.
APA
Liu, C., He, Y., Li, X., Li, R., He, K., & Wang, L. (2014). Inhibition of serine/threonine protein phosphatase PP1 protects cardiomyocytes from tunicamycin‑induced apoptosis and I/R through the upregulation of p-eIF2α. International Journal of Molecular Medicine, 33, 499-506. https://doi.org/10.3892/ijmm.2013.1603
MLA
Liu, C., He, Y., Li, X., Li, R., He, K., Wang, L."Inhibition of serine/threonine protein phosphatase PP1 protects cardiomyocytes from tunicamycin‑induced apoptosis and I/R through the upregulation of p-eIF2α". International Journal of Molecular Medicine 33.3 (2014): 499-506.
Chicago
Liu, C., He, Y., Li, X., Li, R., He, K., Wang, L."Inhibition of serine/threonine protein phosphatase PP1 protects cardiomyocytes from tunicamycin‑induced apoptosis and I/R through the upregulation of p-eIF2α". International Journal of Molecular Medicine 33, no. 3 (2014): 499-506. https://doi.org/10.3892/ijmm.2013.1603
Copy and paste a formatted citation
x
Spandidos Publications style
Liu C, He Y, Li X, Li R, He K and Wang L: Inhibition of serine/threonine protein phosphatase PP1 protects cardiomyocytes from tunicamycin‑induced apoptosis and I/R through the upregulation of p-eIF2α. Int J Mol Med 33: 499-506, 2014.
APA
Liu, C., He, Y., Li, X., Li, R., He, K., & Wang, L. (2014). Inhibition of serine/threonine protein phosphatase PP1 protects cardiomyocytes from tunicamycin‑induced apoptosis and I/R through the upregulation of p-eIF2α. International Journal of Molecular Medicine, 33, 499-506. https://doi.org/10.3892/ijmm.2013.1603
MLA
Liu, C., He, Y., Li, X., Li, R., He, K., Wang, L."Inhibition of serine/threonine protein phosphatase PP1 protects cardiomyocytes from tunicamycin‑induced apoptosis and I/R through the upregulation of p-eIF2α". International Journal of Molecular Medicine 33.3 (2014): 499-506.
Chicago
Liu, C., He, Y., Li, X., Li, R., He, K., Wang, L."Inhibition of serine/threonine protein phosphatase PP1 protects cardiomyocytes from tunicamycin‑induced apoptosis and I/R through the upregulation of p-eIF2α". International Journal of Molecular Medicine 33, no. 3 (2014): 499-506. https://doi.org/10.3892/ijmm.2013.1603
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