Cathepsin D is involved in the oxygen and glucose deprivation/reperfusion-induced apoptosis of astrocytes

  • Authors:
    • Jianlin Liu
    • Lin Yang
    • Hongyan Tian
    • Qiang Ma
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  • Published online on: August 18, 2016     https://doi.org/10.3892/ijmm.2016.2709
  • Pages: 1257-1263
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Abstract

The lysosome and its associated protein cathe­psin D (Cat D) play critical roles in the pathological process of secondary damage following ischemia/reperfusion (I/R) injury. However, the roles of Cat D in I/R-exposed astrocytesremain unclear. In this study, we determined the roles of Cat D in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced apoptosis of astrocytes as well as the underlying mechanisms. We found that OGD/R markedly increased cell apoptosis and the production of inflammatory cytokines, namely IL-6, tumor necrosis factor (TNF)-α and FasL in a reperfusion time‑dependent manner and their elevation peaked at 24 h after reperfusion. Moreover, the cytosolic Cat D level and Cat D activity was significantly upregulated in response to OGD/R exposure. Furthermore, OGD/R exposure gradually disrupted the innate acidic conditions of the lysosome. Exogenous TNF-α and FasL administration elevated cytosolic Cat D levels and cell apoptosis whereas TNFR1 and Fas inhibition significantly reversed these effects induced by OGD/R. Cat D overexpression enhanced cell apoptosis and the levels of apoptogenic proteins, including Bax and caspase-3, whereas Cat D siRNA transfection had an inhibitory effect on cell apoptosis and the expression of proapoptotic proteins. In addition, we observed that Cat D upregulation disrupted mitochondrial membrane potential and induced the production of reactive oxygen species. In conclusion, OGD/R injury induced the production of TNF-α, IL-6 and FasL which promoted lysosomal dysfunction and Cat D leakage into the cytoplasm. This eventually resulted in caspase‑dependent apoptosis, mitochondrial membrane potential loss and oxidative stress in astrocytes.
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October-2016
Volume 38 Issue 4

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

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Spandidos Publications style
Liu J, Yang L, Tian H and Ma Q: Cathepsin D is involved in the oxygen and glucose deprivation/reperfusion-induced apoptosis of astrocytes. Int J Mol Med 38: 1257-1263, 2016
APA
Liu, J., Yang, L., Tian, H., & Ma, Q. (2016). Cathepsin D is involved in the oxygen and glucose deprivation/reperfusion-induced apoptosis of astrocytes. International Journal of Molecular Medicine, 38, 1257-1263. https://doi.org/10.3892/ijmm.2016.2709
MLA
Liu, J., Yang, L., Tian, H., Ma, Q."Cathepsin D is involved in the oxygen and glucose deprivation/reperfusion-induced apoptosis of astrocytes". International Journal of Molecular Medicine 38.4 (2016): 1257-1263.
Chicago
Liu, J., Yang, L., Tian, H., Ma, Q."Cathepsin D is involved in the oxygen and glucose deprivation/reperfusion-induced apoptosis of astrocytes". International Journal of Molecular Medicine 38, no. 4 (2016): 1257-1263. https://doi.org/10.3892/ijmm.2016.2709