| Title | Proteomic analysis uncovers novel actions of the neurosecretory protein VGF in nociceptive processing. | | Author(s) | Riedl MS, Braun PD, Kitto KF, Roiko SA, Anderson LB, Honda CN, Fairbanks CA, Vulchanova L | | Institution | Departments of Neuroscience, Pharmaceutics, Pharmacology, and Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA. | | Source | J Neurosci 2009 Oct 21; 29(42):13377-88. | | MeSH | Animals
Benzoxazoles
Cells, Cultured
Disease Models, Animal
Dose-Response Relationship, Drug
Enzyme Inhibitors
Freund's Adjuvant
Ganglia, Spinal
Hyperalgesia
Imidazoles
Inflammation
Male
Microglia
Neurons, Afferent
Neuropeptides
Nociceptors
Organ Culture Techniques
Pain Measurement
Peptides
Peripheral Nervous System Diseases
Proteomics
Pyridines
Quinolinium Compounds
Rats
Rats, Sprague-Dawley
Reaction Time
Receptor, trkA
Receptors, Purinergic P2
Signal Transduction
Spinal Cord Injuries
Time Factors
Up-Regulation
| | Abstract | Peripheral tissue injury is associated with changes in protein expression in sensory neurons that may contribute to abnormal nociceptive processing. We used cultured dorsal root ganglion (DRG) neurons as a model of axotomized neurons to investigate early changes in protein expression after nerve injury. Comparing protein levels immediately after DRG dissociation and 24 h later by proteomic differential expression analysis, we found a substantial increase in the levels of the neurotrophin-inducible protein VGF (nonacronymic), a putative neuropeptide precursor. In a rodent model of nerve injury, VGF levels were increased within 24 h in both injured and uninjured DRG neurons, and the increase persisted for at least 7 d. VGF was also upregulated 24 h after hindpaw inflammation. To determine whether peptides derived from proteolytic processing of VGF participate in nociceptive signaling, we examined the spinal effects of AQEE-30 and LQEQ-19, potential proteolytic products shown previously to be bioactive. Each peptide evoked dose-dependent thermal hyperalgesia that required activation of the mitogen-activated protein kinase p38. In addition, LQEQ-19 induced p38 phosphorylation in spinal microglia when injected intrathecally and in the BV-2 microglial cell line when applied in vitro. In summary, our results demonstrate rapid upregulation of VGF in sensory neurons after nerve injury and inflammation and activation of microglial p38 by VGF peptides. Therefore, VGF peptides released from sensory neurons may participate in activation of spinal microglia after peripheral tissue injury. | | Language | eng | | Pub Type(s) | In Vitro
Journal Article
Research Support, N.I.H., Extramural
| | PubMed ID | 19846725 |
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