PCSK9 regulates apoptosis in human neuroglioma u251 cells via mitochondrial signaling pathways

Int J Clin Exp Pathol. 2015 Mar 1;8(3):2787-94. eCollection 2015.

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9), belongs to a family of proprotein convertases (PCs), encodes a neural apoptosis-regulated convertase 1. However, the precise role of PCSK9 during glioma cells apoptosis has not been reported. Therefore, we examined the effects of knockdown and overexpression of PCSK9 on apoptosis of human neuroglioma U251 cells, and investigated the underlying mechanisms of apoptosis. We found that PCSK9 regulated cells proliferation as determined by CCK-8 and Hoechst staining analysis. In addition, western blot results showed that PCSK9 siRNA promote apoptosis via activation of caspase-3 and down-regulation of the anti-apoptotic proteins, XIAP and p-Akt, while PCSK9 overexpression inhibited apoptosis. Moreover, PCSK9 siRNA improved the ratio of Bax/Bcl-2 which leads to the release of cytochrome c, while PCSK9 overexpression decreased it. Taken together, these data demonstrate that PCSK9 may regulate apoptosis through mitochondrial pathway and is expected to be a promising therapeutic strategy for the malignant glioma.

Keywords: PCSK9; apoptosis; mitochondrial pathway; neuroglioma.

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Knockdown Techniques
  • Glioma / enzymology*
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Mitochondria / enzymology*
  • Mitochondria / pathology
  • Phosphorylation
  • Proprotein Convertase 9
  • Proprotein Convertases / genetics
  • Proprotein Convertases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Signal Transduction*
  • Time Factors
  • Transfection

Substances

  • Apoptosis Regulatory Proteins
  • Proto-Oncogene Proteins c-akt
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases