Proteomics study of neuropathic and nonneuropathic dorsal root ganglia: altered protein regulation following segmental spinal nerve ligation injury

Komori, Naoka; Takemori, Nobuaki; Kim, Hee Kee; Singh, Anil Kumar; Hwang, Seon‐Hee; Foreman, Robert D.; Chung, Kyungsoon; Chung, Jin Mo; Matsumoto, Hiroyuki

doi:10.1152/physiolgenomics.00255.2006

Cited by 68 publications

(70 citation statements)

References 144 publications

(170 reference statements)

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“…We found that the amount of this protein was 3.25-fold (Table II, spot ID1) higher than that of the sham. Similar results have been found in brain injury detected by microarray (98) and in segmental nerve ligation injury detected by proteomics analysis (99). Interestingly it was found that CPI3 belongs to the subfamily of serpins (100), and its proposed function is to inactivate neuropsin and to control the level of neuropsin in adult mouse brain (101).…”

Section: Discussionsupporting

confidence: 72%

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Tsai¹,

Shen²,

Kuo

et al. 2008

Molecular & Cellular Proteomics

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Acidic fibroblast growth factor (aFGF; also known as FGF-1) is a potent neurotrophic factor that affects neuronal survival in the injured spinal cord. However, the pathological changes that occur with spinal cord injury (SCI) and the attribution to aFGF of a neuroprotective effect during SCI are still elusive. In this study, we demonstrated that rat SCI, when treated with aFGF, showed significant functional recovery as indicated by the Basso, Beattie, and Bresnahan locomotor rating scale and the combined behavior score (p < 0.01-0.001). Furthermore proteomics and bioinformatics approaches were adapted to investigate changes in the global protein profile of the damaged spinal cord tissue when experimental rats were treated either with or without aFGF at 24 h after injury. We found that 51 protein spots, resolvable by two-dimensional PAGE, had significant differential expression. Using hierarchical clustering analysis, these proteins were categorized into five major expression patterns. Noticeably proteins involved in the process of secondary injury, such as astrocyte activation (glial fibrillary acidic protein), inflammation (S100B), and scar formation (keratan sulfate proteoglycan lumican), which lead to the blocking of injured spinal cord regeneration, were down-regulated in the contusive spinal cord after treatment with aFGF. We propose that aFGF might initiate a series of biological processes to prevent or attenuate secondary injury and that this, Spinal cord injury (SCI)1 is a costly disease as well as the most frequent cause of mortality and morbidity in every medical care system around the world (1, 2). Traumatic axonal injury is a primary sequela of contusive SCI and is characterized by axonal swelling and disconnection of the ascending sensory and descending motor tracts (3). Contusive SCI seems to initiate a complicated cascade of pathophysiological changes, a process called secondary injury, including fiber deformation, increased vascular permeability, local ischemia, intraneuronal edema, and local demyelination. Moreover traumatic axonal injury typically involves a disruption of the axonal membrane, and this results in up-regulation of the entry of calcium, the influx of which initiates calpain activation (4, 5) and mitochondrial injury/swelling (6), resulting in cytochrome c release and caspase activation (7). Simultaneously the proliferation and hypertrophy of astrocytes around the injury site are characterized by increased immunoreactivity to glial fibrillary acidic proteins (GFAPs) (8).Although many studies have focused on revealing the pathophysiology of SCI, the exact molecular mechanisms and the biochemical pathways that mediate secondary injury remain sketchy (9). Spinal cord injury often causes permanent neurological deficits mostly because the injured neurons lack regenerative ability, and the series of destructive processes that follow SCI results in a second wave of cell death and spreading tissue loss (10). Therefore, studies of the stimulaFrom the ‡Institute

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Section: Discussionsupporting

confidence: 72%

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Tsai¹,

Shen²,

Kuo

et al. 2008

Molecular & Cellular Proteomics

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“…The regulation of multiple neuronal signalling pathways as a coordinated response to nerve injury can occur at the transcriptional level (Costigan et al 2002;Zhang and Xiao 2005;Persson et al 2009) and the post-transcriptional level (Komori et al 2007;Zhang et al 2008;Li et al 2009). Post-transcriptional gene silencing is now thought to regulate a majority of mammalian genes.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-143 expression in dorsal root ganglion neurons

et al. 2011

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The unpleasant sensory and emotional experience of pain is initiated by excitation of primary afferent nociceptive neurons. Nerve damage or inflammation induces changes in nociceptive DRG neurons which contribute to both peripheral and central sensitization of pain-sensitive pathways. Recently, blockade of microRNA synthesis has been found to modulate the response of nociceptive neurons to inflammatory stimuli. However, little is known about the contributions of individual miRNAs to painful conditions. We compared miRNA expression in mouse sensory neurons and focussed on the localisation and control of miR-143. Using miRNA-arrays we compared the microRNA expression profile of intact lumbar DRG with one-day-old DRG cultures and found that nine miRNAs including miR-143 showed lower expression levels in cultures. Subsequent RT-qPCR confirmed array data and in-situ hybridisation localised miR-143 in the cytosol of sensory DRG neurons in situ and in vitro. Analysis of microbead-enriched neuron cultures showed significantly higher expression levels of miR-143 in isolectin B4 (I-B4) binding sensory neurons compared with neurons in the I-B4 negative flow-through fraction. In animal models of peripheral inflammation (injection of Complete Freund's Adjuvant, CFA) and nerve damage (transection of the sciatic nerve), we found that expression levels of miR-143 were significantly lower in DRGs ipsilateral to CFA injection or after nerve damage. Taken together, our data demonstrate for the first time miR-143 expression in nociceptive neurons. Since expression levels of miR-143 were higher in I-B4 positive neurons and declined in response to inflammation but not axotomy, miR-143 could selectively contribute to mRNA regulation in specific populations of nociceptors.

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“…Therefore, it is conceivable that several metabolic enzymes were detected in the present study. Aldolase C is also differentially expressed in a number of neuropathic pain models (25)(26)(27). Therefore, our data suggest that the regulation of metabolic enzymes are involved in pain development and the analgesic effects of EA.…”

Section: Discussionmentioning

confidence: 58%

Phosphoproteomic analysis of electroacupuncture analgesia in an inflammatory pain rat model

Lee

Kim

et al. 2012

Mol Med Report

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Abstract. The phosphorylation changes of nociceptive signaling proteins in the spinal cord dorsal horn (SCDH) are important in creating exaggerated pain following peripheral inflammation. Electroacupuncture (EA) has been widely used to relieve acute and chronic inflammatory pain in human and experimental pain models. In the present study, we performed a phosphoproteomic analysis to investigate whether EA alters protein phosphorylation in SCDH to attenuate pain development. Inflammatory hyperalgesia was induced by intraplantar injection of complete Freund's adjuvant (CFA) into the rat hind paw. EA treatment at ST36 and SP6 acupoints alleviated thermal hyperalgesia of the CFA-induced inflammatory pain model rats. The SCDH proteins from the control, inflammatory pain model and EA treatment rats were separated by 2-dimensional gel electrophoresis and the alterations in phosphoproteins were detected by Pro-Q Diamond staining. Eight proteins were differentially phosphorylated following EA treatment in the inflammatory pain model. Aldolase C, nascent polypeptide-associated complex α, stress-induced phosphoprotein 1 and heat shock protein 90 were identified as phosphoproteins whose expression was increased, whereas GDP dissociation inhibitor 1, thiamine triphosphatase, phosphoglycerate kinase 1 and 14-3-3 γ were phosphoproteins whose expression was decreased. This is the first phosphoproteomic screening study to elucidate the working mechanisms of EA analgesia. The results suggest that the regulation of cellular pathways in which the identified proteins are involved may be associated with an EA analgesic mechanism. IntroductionPeripheral inflammation frequently leads to the development of chronic pain, which is a leading cause of disability globally. In inflammatory pain, peripheral stimuli activate primary afferent neurons and are transmitted to secondary sensory neurons in the spinal cord dorsal horn (SCDH). Persistent noxious stimuli increase the excitability of secondary neurons in the SCDH and decrease the pain threshold. Early studies attributed this central sensitization to the facilitated synaptic transmission of nociceptive signals in the SCDH (1,2). Various signaling molecules such as glutamate receptors, protein kinase A (PKA), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), Ca 2+ -/calmodulin-dependent kinase II (CaMKII) and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-jun N-terminal kinase (JNK), have been shown to be involved in altered nociceptive processing in the SCDH (3-5). Activation of these molecules is capable of inducing signaling cascades that lead to the subsequent expression of pain-associated genes such as prodynorphin, neurokinin-1 (NK-1) and cyclooxygenase-2 (COX-2) (6,7).Acupuncture, a traditional therapeutic method in oriental medicine, has long been clinically used to relieve pain. In particular, electroacupuncture (EA), where electrical stimulation is applied to acupuncture needles, is widely used in clinical an...

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Proteomics study of neuropathic and nonneuropathic dorsal root ganglia: altered protein regulation following segmental spinal nerve ligation injury

Cited by 68 publications

References 144 publications

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

MicroRNA-143 expression in dorsal root ganglion neurons

Phosphoproteomic analysis of electroacupuncture analgesia in an inflammatory pain rat model

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