Overexpression of LIM kinase 1 renders resistance to apoptosis in PC12 cells by inhibition of caspase activation

Cell Mol Neurobiol. 2004 Apr;24(2):181-92. doi: 10.1023/b:cemn.0000018615.84358.33.

Abstract

LIM kinases (LIMKs) regulate actin polymerization by phosphorylating cofilin and are predominantly expressed in neural tissue. In this study, the effect of LIMK1 overexpression in PC12 cell apoptosis was investigated. PC12 cells overexpressing the wild-type LIMK1 were more resistant to serum-withdrawal-induced cell death and the level of caspase 3 activation in these cells was lower than in the control PC12 cells or than in the PC12 cells expressing a mutant LIMK1 lacking the kinase domain. The inhibition of JNK activation was observed in the PC12 cells overexpressing the wild-type LIMK1 after serum withdrawal. These results suggest that the LIMK1 might allow resistance to apoptosis in PC12 cells by inhibiting JNK activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Depolymerizing Factors
  • Animals
  • Apoptosis / physiology*
  • Caspase 3
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Cell Survival / genetics
  • Culture Media, Serum-Free / pharmacology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation
  • JNK Mitogen-Activated Protein Kinases
  • Lim Kinases
  • Microfilament Proteins / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Mutation / genetics
  • Neurodegenerative Diseases / enzymology
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / physiopathology
  • Neurons / enzymology
  • PC12 Cells
  • Phosphorylation
  • Protein Kinases
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Structure, Tertiary / genetics
  • Rats
  • Up-Regulation / genetics

Substances

  • Actin Depolymerizing Factors
  • Caspase Inhibitors
  • Culture Media, Serum-Free
  • DNA-Binding Proteins
  • Microfilament Proteins
  • Protein Kinases
  • Lim Kinases
  • Limk1 protein, rat
  • Protein Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Casp3 protein, rat
  • Caspase 3
  • Caspases