Nerve growth factor enhances the excitability of rat sensory neurons through activation of the atypical protein kinase C isoform, PKMζ

Zhang, YiHong; Kays, Joanne; Hodgdon, K. E.; Nicol, Grant D.

doi:10.1152/jn.00030.2011

Cited by 33 publications

(60 citation statements)

References 109 publications

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“…To date there has not been any characterization of PKC isoform expression in vagal sensory neurons, although PKC expression in somatosensory DRG neurons indicates that, at a minimum, b1, b2, d, «, and z are expressed in complex combinatorial patterns (Cesare et al, 1999;Wu et al, 2012). Similar to our findings, PKC has repeatedly been shown to play a role in inflammation-induced hyperexcitability in nociceptive DRG (Cesare et al, 1999;Baker, 2005;Wu et al, 2012;Zhang et al, 2012). It is known that PMA binds to the same enzyme subsite as DAG, and thus PMA activates only classic and novel PKC isoforms, suggesting that PKC expression is not limited to atypical isoforms in vagal sensory nerves.…”

supporting

confidence: 86%

“…Upon activation, PKC translocates to the plasma membrane, in which it engages in phosphorylation of a wide variety of protein targets. Given that previous studies demonstrated multiple isoforms of PKC heterogeneously expressed throughout the somatosensory DRG neuronal population (Cesare et al, 1999;Hayase et al, 2007;Wu et al, 2012;Zhang et al, 2012) and that PKC isoform expression has not yet been characterized in vagal neurons, we decided in this study to observe global PKC translocation using a pan-PKC antibody that would detect all PKC isoforms. All vagal neurons were immunoreactive for PKC with no fluorescent signal observed in the absence of primary antibody (data not shown).…”

Section: Resultsmentioning

confidence: 99%

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Sensory Nerve Terminal Mitochondrial Dysfunction Induces Hyperexcitability in Airway Nociceptors via Protein Kinase C

Hadley

Bahia

Taylor‐Clark

2014

Molecular Pharmacology

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Airway sensory nerve excitability is a key determinant of respiratory disease-associated reflexes and sensations such as cough and dyspnea. Inflammatory signaling modulates mitochondrial function and produces reactive oxygen species (ROS). Peripheral terminals of sensory nerves are densely packed with mitochondria; thus, we hypothesized that mitochondrial modulation would alter neuronal excitability. We recorded action potential firing from the terminals of individual bronchopulmonary C-fibers using a mouse ex vivo lung-vagal ganglia preparation. C-fibers were characterized as nociceptors or non-nociceptors based upon conduction velocity and response to transient receptor potential (TRP) channel agonists. Antimycin A (mitochondrial complex III Q i site inhibitor) had no effect on the excitability of non-nociceptors. However, antimycin A increased excitability in nociceptive C-fibers, decreasing the mechanical threshold by 50% and increasing the action potential firing elicited by a P2X 2/3 agonist to 270% of control. Antimycin A-induced nociceptor hyperexcitability was independent of TRP ankyrin 1 or TRP vanilloid 1 channels. Blocking mitochondrial ATP production with oligomycin or myxothiazol had no effect on excitability. Antimycin A-induced hyperexcitability was dependent on mitochondrial ROS and was blocked by intracellular antioxidants. ROS are known to activate protein kinase C (PKC). Antimycin A-induced hyperexcitability was inhibited by the PKC inhibitor bisindolylmaleimide (BIM) I, but not by its inactive analog BIM V. In dissociated vagal neurons, antimycin A caused ROS-dependent PKC translocation to the membrane. Finally, H 2 O 2 also induced PKC-dependent nociceptive C-fiber hyperexcitability and PKC translocation. In conclusion, ROS evoked by mitochondrial dysfunction caused nociceptor hyperexcitability via the translocation and activation of PKC.

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supporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Sensory Nerve Terminal Mitochondrial Dysfunction Induces Hyperexcitability in Airway Nociceptors via Protein Kinase C

Hadley

Bahia

Taylor‐Clark

2014

Molecular Pharmacology

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“…Furthermore, PKC not only acts as a second messenger but BDNF and NGF also modulate the activity of PKC [96,97]. PKC, in turn, influence the expression of NTFs, such as NGF [98], BDNF [99], and glial cell line-derived neurotrophic factor [100].…”

Section: Downstream Targets Of Pkcmentioning

confidence: 99%

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

et al. 2017

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Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC. Moreover, we discuss the role of PKC on synaptogenesis and neuroplasticity in the context of BD. The recent development of animal models of BD, such as stimulant-treated and paradoxical sleep deprivation, and the ability to intervene pharmacologically provide further insights into the involvement of PKC in BD. In addition, the effect of PKC inhibitors, such as tamoxifen, in the resolution of manic symptoms in patients with BD further points in that direction. Furthermore, a wide variety of growth factors influence neurotransmission through several molecular pathways that involve downstream effects of PKC. Our current understanding identifies the PKC pathway as a potential therapeutic avenue for BD.

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“…The siRNA sequence targeting rat PKMζ, 5′-GCAAGCTGCTTGTCCATAAAC-3′, has been shown previously to efficiently downregulate rat PKMζ expression (50). Pairs of complementary oligonucleotides containing these sequences were synthesized and cloned into the pGMLV-SB1 lentivector.…”

Section: Lentiviral Shrna-mediated Knockdown Of Hippocampal Pkmζmentioning

confidence: 99%

Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis

Dong¹,

Han²,

Li³

et al. 2014

J. Clin. Invest.

160

128

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Nerve growth factor enhances the excitability of rat sensory neurons through activation of the atypical protein kinase C isoform, PKMζ

Abstract: Zhang YH, Kays J, Hodgdon KE, Sacktor TC, Nicol GD. Nerve growth factor enhances the excitability of rat sensory neurons through activation of the atypical protein kinase C isoform, PKM.

Cited by 33 publications

References 109 publications

Sensory Nerve Terminal Mitochondrial Dysfunction Induces Hyperexcitability in Airway Nociceptors via Protein Kinase C

Sensory Nerve Terminal Mitochondrial Dysfunction Induces Hyperexcitability in Airway Nociceptors via Protein Kinase C

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis

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