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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

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

Published on: January 7, 2013

Okadaic acid interferes with phorbol-ester-mediated down-regulation of protein kinase C-alpha, C-delta and C-epsilon

A Gatti1, P J Robinson

  • 1Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. andrea@pop.ucr.edu

European Journal of Biochemistry
|November 18, 1997
PubMed

Insights

Protein kinase C (PKC) down-regulation by phorbol esters is partially prevented by okadaic acid, suggesting phosphorylation protects PKC. This indicates okadaic acid

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Prolonged exposure to tumor-promoting phorbol esters causes protein kinase C (PKC) inactivation and degradation (down-regulation).
  • Distinct PKC-alpha forms exist in PC12 cells, with differential responses to phorbol ester treatment.

Purpose of the Study:

  • To investigate the relationship between PKC-alpha phosphorylation and its down-regulation.
  • To explore the role of protein phosphatases in PKC regulation.

Main Methods:

  • Utilized one- and two-dimensional immunoblot analyses.
  • Exposed PC12 cells to phorbol ester and okadaic acid (a protein phosphatase inhibitor).
  • Examined the effects on PKC-alpha, PKC-delta, and PKC-epsilon.

Main Results:

  • Okadaic acid partially protected PKC-alpha against phorbol-ester-mediated down-regulation.
  • A similar protective effect was observed for PKC-delta and PKC-epsilon.
  • These findings suggest a role for phosphorylation in preventing PKC down-regulation.

Conclusions:

  • PKC phosphorylation may be a key mechanism protecting against phorbol-ester-induced down-regulation.
  • The tumor-promoting activity of okadaic acid might stem from sustained PKC phosphorylation.
  • This study elucidates a novel regulatory pathway for PKC activity and stability.

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