Two isoforms of cyclic GMP-dependent kinase-I exhibit distinct expression patterns in the adult mouse dorsal root ganglion

Mol Pain. 2018 Jan-Dec:14:1744806918796409. doi: 10.1177/1744806918796409.

Abstract

cGMP-dependent kinase-I (cGKI) is known to regulate spinal pain processing. This enzyme consists of two isoforms (cGKIα and cGKIβ) that show distinct substrate specificity and tissue distribution. It has long been believed that the α isoform is exclusively expressed in the adult dorsal root ganglion. The aim of the present study was to reexamine the expression of cGKI isoforms in the adult mouse dorsal root ganglion using isoform-specific cGKI antibodies whose specificities had been validated in the previous studies. Immunoblot and immunohistochemical analyses revealed the presence of both isoforms in the dorsal root ganglion. Moreover, cGKIα was found to be mainly expressed within the cytoplasm of small- to medium-sized peptidergic and nonpeptidegic C-fibers, whereas cGKIβ was located within the nuclei of a wide range of dorsal root ganglion neurons. In addition, glutamine synthetase-positive satellite glial cells expressed both isoforms to varying degrees. Finally, using an experimental model for neuropathic pain produced by L5 spinal nerve transection, we found that cGKIα expression was downregulated in the injured, but not in the uninjured, dorsal root ganglion. In contrast, cGKIβ expression was upregulated in both the injured and uninjured dorsal root ganglions. Also, injury-induced cGKIβ upregulation was found to occur in small-to-medium-diameter dorsal root ganglion neurons. These data thus demonstrate the existence of two differently distributed cGKI isoforms in the dorsal root ganglion, and may provide insight into the cellular and molecular mechanisms of pain.

Keywords: Cyclic GMP-dependent kinase-I; dorsal root ganglion; gene expression; peripheral nerve injury; satellite glial cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Cyclic GMP-Dependent Protein Kinase Type I / genetics
  • Cyclic GMP-Dependent Protein Kinase Type I / metabolism*
  • Disease Models, Animal
  • Ganglia, Spinal / metabolism*
  • Gene Expression Regulation / physiology*
  • Glutamate-Ammonia Ligase / metabolism
  • Lectins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Fibers / pathology
  • Nerve Tissue Proteins / metabolism
  • Neuralgia / pathology*
  • Protein Isoforms / metabolism*

Substances

  • Lectins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Cyclic GMP-Dependent Protein Kinase Type I
  • Glutamate-Ammonia Ligase
  • Calcitonin Gene-Related Peptide