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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Activation of PKC is sufficient to induce an apoptotic program in salivary gland acinar cells

M E Reyland1, K A Barzen, S M Anderson

  • 1Department of Basic Science and Oral Research, School of Dentistry, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado, CO 80262, USA. mary.reyland@uchsc.edu

Cell Death and Differentiation
|February 15, 2001
PubMed

Insights

Activation of protein kinase C (PKC) with 12-O-tetradecanoyl phorbol-13-ester (TPA) triggers apoptosis in salivary cells. Calpain inhibition enhances this TPA-induced cell death, highlighting PKC

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Specific protein kinase C (PKC) isoforms are implicated in promoting apoptosis.
  • The role of PKC activation in salivary acinar cell apoptosis requires further elucidation.

Purpose of the Study:

  • To investigate the role of PKC activation in inducing apoptosis in salivary acinar cells.
  • To determine the involvement of specific PKC isoforms and signaling pathways in this process.

Main Methods:

  • Treatment of salivary acinar cells with 12-O-tetradecanoyl phorbol-13-ester (TPA) to activate PKC.
  • Assessment of apoptosis using DNA fragmentation and caspase-3 activation assays.
  • Pretreatment with calpain inhibitor (calpeptin) to modulate TPA effects.
  • Immunoblot analysis of PKC isoform expression and subcellular localization.
  • Analysis of c-jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathway activation.

Main Results:

  • TPA-induced apoptosis in salivary acinar cells, evidenced by DNA fragmentation and caspase-3 activation.
  • Calpeptin pretreatment enhanced TPA-induced apoptosis, DNA fragmentation, and caspase-3 activation.
  • Calpeptin delayed TPA-induced downregulation of PKC alpha and PKC delta, increasing their membrane presence.
  • TPA triggered biphasic JNK activation and ERK inactivation.
  • Expression of constitutively active PKC alpha or PKC delta induced apoptosis, but not PKC epsilon.

Conclusions:

  • PKC activation is sufficient to initiate an apoptotic program in salivary acinar cells.
  • Specific PKC isoforms, particularly PKC alpha and PKC delta, play a critical role in TPA-induced apoptosis.
  • Calpain inhibition can potentiate PKC-mediated apoptosis in these cells.

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