Protein kinase C δ (PKCδ) splice variants modulate apoptosis pathway in 3T3L1 cells during adipogenesis: identification of PKCδII inhibitor

J Biol Chem. 2013 Sep 13;288(37):26834-46. doi: 10.1074/jbc.M113.482638. Epub 2013 Jul 31.

Abstract

Increased food intake and lack of physical activity results in excess energy stored in adipocytes, and this imbalance contributes to obesity. New adipocytes are required for storage of energy in the white adipose tissue. This process of adipogenesis is widely studied in differentiating 3T3L1 preadipocytes in vitro. We have identified a key signaling kinase, protein kinase C delta (PKCδ), whose alternative splice variant expression is modulated during adipogenesis. We demonstrate that PKCδII splice variant promotes survival in differentiating 3T3L1 cells through the Bcl2 pathway. Here we demonstrate that resveratrol, a naturally occurring polyphenol, increases apoptosis and inhibits adipogenesis along with disruption of PKCδ alternative splicing during 3T3L1 differentiation. Importantly, we have identified a PKCδII splice variant inhibitor. This inhibitor may be a valuable tool with therapeutic implications in obesity.

Keywords: Adipogenesis; Alternative Splicing; Obesity; Protein Kinase C (PKC); Resveratrol.

Publication types

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

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis*
  • Alternative Splicing*
  • Animals
  • Apoptosis*
  • Cell Differentiation
  • Gene Expression Regulation, Enzymologic
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Polyphenols / chemistry
  • Protein Kinase C-delta / antagonists & inhibitors*
  • Protein Kinase C-delta / genetics
  • Protein Kinase Inhibitors / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Resveratrol
  • Stilbenes / chemistry*
  • Transfection

Substances

  • Polyphenols
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Stilbenes
  • Protein Kinase C-delta
  • Resveratrol