Brain research. Molecular brain research
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Brain Res. Mol. Brain Res. · Feb 2003
Sensory neuron proteins interact with the intracellular domains of sodium channel NaV1.8.
Voltage-gated sodium channels initiate and propagate action potentials in excitable cells. The tetrodotoxin-resistant Na(+) channel (Na(V)1.8/SNS) is expressed in damage-sensing neurons (nociceptors) and plays an important role in pain pathways. Expression of high levels of functional Na(V)1.8 in heterologous cells has proved problematic, even in the presence of known sodium channel accessory beta-subunits. ⋯ Many clones are expressed at high levels in small diameter DRG neurons as judged by in situ hybridization. Interacting proteins include cytoplasmic elements and linker proteins (e.g. beta-actin and moesin), enzymes (e.g. inositol polyphosphate 5-phosphatase and TAO2 thousand and one protein kinase), channels and membrane-associated proteins (voltage-dependent anion channel VDAC3V and tetraspanin), as well as motor proteins (dynein intermediate and light chain) and transcripts encoding previously undescribed proteins. Immunoprecipitation (pull-down) assays confirm that some of the proteins interact with, and may hence regulate, Na(V)1.8 in vivo.
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Brain Res. Mol. Brain Res. · Feb 2003
Abnormal PI3 kinase/Akt signal pathway in vagal afferent neurons and vagus nerve of streptozotocin-diabetic rats.
The PI3 (phosphatidylinositol-3) kinase/Akt (protein kinase B) signal pathway is involved in the molecular signaling that regulates retrograde axonal transport of neurotrophins in the nervous system. Previous work showed that a reduced retrograde axonal transport of endogenous nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the vagus nerve of diabetic rats occurred in the presence of normal production of neurotrophins and neurotrophin receptors. To assess the potential involvement of an impaired PI3 kinase/Akt signal pathway in the diabetes-induced reduction in retrograde axonal transport of neurotrophins in the vagus nerve, we characterized diabetes-induced changes in the PI3 kinase/Akt signal pathway in the vagus nerve and vagal afferent neurons. ⋯ In contrast, there was a significant increase in the phosphorylation of p70s6 kinase (thr421/ser424) along with a normal protein expression of p70s6 kinase in the vagus nerve of diabetic rats. However, diabetes induced an overall decrease in immunoreactivity of the p85 subunit of PI3 kinase, phospho-Akt (ser473) and phospho-p70s6/p85s6 kinase (thr421/ser424) in vagal afferent neurons. Thus, impaired PI3 kinase/Akt signal pathway may partly account for the reduced retrograde axonal transport of neurotrophins in the vagus nerve of STZ-induced diabetic rats.