Effect of protein kinase C on endoplasmic reticulum cholesterol

Biochem Biophys Res Commun. 2002 Jan 11;290(1):488-93. doi: 10.1006/bbrc.2001.6156.

Abstract

Plasma membrane cholesterol both regulates and is regulated by effector proteins in the endoplasmic reticulum (ER) through a feedback system that is poorly understood. We now show that ER cholesterol varies over a fivefold range in response to experimental agents that act upon protein kinase C (PKC). Agents that activate Ca(2+)-dependent PKC [phorbol-12-myristate-13-acetate (PMA) and bryostatin 1] increased the level of ER cholesterol; inhibitors such as staurosporine and calphostin C decreased it. Rottlerin, a selective inhibitor of the PKC-delta isoform, also increased ER cholesterol. The esterification of plasma membrane cholesterol was altered by protein kinase C-directed agents in a corresponding fashion. Furthermore, the regulatory effect of plasma membrane cholesterol on the esterification of ER cholesterol was blocked by PKC-directed agents. These findings suggest that multiple protein kinase C isoforms participate in the regulation of ER cholesterol and therefore in cholesterol homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetophenones / pharmacology
  • Benzopyrans / pharmacology
  • Bryostatins
  • Calcium / metabolism
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cholesterol / chemistry
  • Cholesterol / metabolism*
  • Dose-Response Relationship, Drug
  • Endoplasmic Reticulum / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / metabolism
  • Humans
  • Lactones / pharmacology
  • Macrolides
  • Mitogens / pharmacology
  • Naphthalenes / pharmacology
  • Protein Isoforms
  • Protein Kinase C / metabolism
  • Protein Kinase C / pharmacology*
  • Protein Kinase C / physiology*
  • Staurosporine / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Acetophenones
  • Benzopyrans
  • Bryostatins
  • Enzyme Inhibitors
  • Lactones
  • Macrolides
  • Mitogens
  • Naphthalenes
  • Protein Isoforms
  • bryostatin 1
  • Cholesterol
  • rottlerin
  • Protein Kinase C
  • Staurosporine
  • calphostin C
  • Tetradecanoylphorbol Acetate
  • Calcium