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Suppression of apoptosis in the protein kinase Cdelta null mouse in vivo

Michael J Humphries1, Kirsten H Limesand, Jonathan C Schneider

  • 1Department of Craniofacial Biology and School of Dentistry, University of Colorado Health Sciences Center, Aurora, Colorado 80262, USA.

The Journal of Biological Chemistry
|February 3, 2006
PubMed

Insights

Loss of Protein Kinase C delta (PKCdelta) protects salivary glands from gamma-irradiation-induced apoptosis. PKCdelta functions downstream of p53 but upstream of c-Jun amino-terminal kinase in this process.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Protein Kinase C delta (PKCdelta) is crucial for mitochondrial-dependent apoptosis in epithelial cells.
  • Understanding PKCdelta's role in DNA damage response is vital for radiation protection strategies.

Purpose of the Study:

  • To investigate if PKCdelta deficiency protects salivary glands from gamma-irradiation-induced apoptosis in vivo.
  • To elucidate the molecular mechanism by which PKCdelta influences apoptosis.

Main Methods:

  • Utilized PKCdelta knockout (PKCdelta(-/-)) mice and wild-type (PKCdelta(+/+)) littermates.
  • Assessed apoptosis via gamma-irradiation and etoposide treatment in vivo and in vitro.
  • Analyzed key apoptotic markers: cytochrome c release, PARP cleavage, caspase-3 activation, p53, and c-Jun amino-terminal kinase (JNK) activation.

Main Results:

  • PKCdelta(-/-) mice exhibited significantly suppressed apoptosis (>60%) in parotid glands after gamma-irradiation compared to wild-type.
  • PKCdelta(-/-) cells showed impaired mitochondrial apoptosis, which was reversible upon PKCdelta reintroduction.
  • PKCdelta functions downstream of p53 activation but upstream of JNK activation in DNA damage-induced apoptosis.

Conclusions:

  • PKCdelta plays an essential role in mediating DNA damage-induced apoptosis in salivary glands.
  • Targeting PKCdelta may offer a protective strategy against radiation-induced salivary gland damage.

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