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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Downregulating PKC delta provides a PI3K/Akt-independent survival signal that overcomes apoptotic signals generated

Minghao Zhong1, Zhimin Lu, David A Foster

  • 1Department of Biological Sciences, Hunter College of The City University of New York, NY 10021, USA.

Oncogene
|February 19, 2002
PubMed

Insights

Overexpression of c-Src in rat fibroblasts induces apoptosis upon serum withdrawal. Downregulation of protein kinase C delta (PKC delta) suppresses this apoptosis through a novel survival pathway.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • c-Src tyrosine kinase overexpression transforms cells.
  • Protein Kinase C delta (PKC delta) is downregulated during transformation by c-Src.
  • Apoptosis is programmed cell death crucial for development and disease.

Purpose of the Study:

  • To investigate the role of c-Src and PKC delta in apoptosis.
  • To identify survival pathways activated by PKC delta downregulation in transformed cells.

Main Methods:

  • Utilized 3Y1 rat fibroblasts engineered to overexpress c-Src.
  • Induced apoptosis via serum withdrawal.
  • Assessed apoptosis using cytochrome c and caspase 9 pathways.
  • Manipulated PKC delta levels and analyzed effects on apoptosis.
  • Investigated the involvement of the PI3K/Akt pathway.

Main Results:

  • 3Y1 cells overexpressing c-Src underwent apoptosis upon serum withdrawal.
  • This apoptosis was mediated by the cytochrome c/caspase 9 pathway.
  • Downregulation of PKC delta suppressed serum withdrawal-induced apoptosis in 3Y1(c-Src) cells.
  • The survival signal from PKC delta downregulation was independent of the PI3K/Akt pathway.

Conclusions:

  • c-Src overexpression sensitizes cells to apoptotic stress.
  • PKC delta downregulation confers a novel survival signal.
  • This survival mechanism is independent of the PI3K/Akt pathway, offering new therapeutic targets.

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