Expression of cyclin-dependent kinase 5 and its activator p35 in models of induced apoptotic death in neurons of the substantia nigra in vivo

J Neurochem. 2001 Jun;77(6):1611-25. doi: 10.1046/j.1471-4159.2001.00376.x.

Abstract

Cyclin-dependent kinase 5 is predominantly expressed in postmitotic neurons and plays a role in neurite elongation during development. It has also been postulated to play a role in apoptosis in a variety of cells, including neurons, but little is known about the generality and functional significance of cdk5 expression in neuronal apoptosis in living brain. We have therefore examined its expression and that of its known activators, p35, p39 and p67, in models of induced apoptosis in neurons of the substantia nigra. We find that cdk5 is expressed in apoptotic profiles following intrastriatal injection of 6-hydroxydopamine and axotomy. It is expressed exclusively in profiles which are in late morphologic stages of apoptosis. In these late stages, derivation of the profiles from neurons, and localization of expression to the nucleus, can be demonstrated by co-labeling with a neuron-specific nuclear marker, NeuN. In another model of induced apoptotic death in nigra, produced by developmental striatal lesion, kinase activity increases in parallel with cell death. While mRNAs for all three cdk5 activators are expressed in nigra during development, only p35 protein is expressed in apoptotic profiles. We conclude that cdk5/p35 expression is a general feature of apoptotic neuron death in substantia nigra neurons in vivo.

Publication types

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

MeSH terms

  • Animals
  • Antibodies
  • Apoptosis / physiology*
  • Axotomy
  • Cyclin-Dependent Kinase 5
  • Cyclin-Dependent Kinases / genetics*
  • Cyclin-Dependent Kinases / metabolism
  • Epitopes / analysis
  • Epitopes / immunology
  • Gene Expression Regulation, Enzymologic
  • Medial Forebrain Bundle / physiology
  • Munc18 Proteins
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neurofilament Proteins / analysis
  • Neurofilament Proteins / immunology
  • Neurons / cytology
  • Neurons / enzymology*
  • Oxidopamine
  • Phosphorylation
  • Quinolinic Acid
  • RNA, Messenger / analysis
  • Rats
  • Substantia Nigra / cytology*
  • Substantia Nigra / metabolism
  • Sympatholytics
  • Vesicular Transport Proteins*
  • tau Proteins / analysis
  • tau Proteins / immunology
  • tau Proteins / metabolism

Substances

  • Antibodies
  • Cdk5 activator p39
  • Epitopes
  • Munc18 Proteins
  • Nerve Tissue Proteins
  • Neurofilament Proteins
  • RNA, Messenger
  • Sympatholytics
  • Vesicular Transport Proteins
  • neuronal Cdk5 activator (p25-p35)
  • tau Proteins
  • Oxidopamine
  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, rat
  • Cyclin-Dependent Kinases
  • Quinolinic Acid