Homeobox gene expression in adult dorsal root ganglia during sciatic nerve regeneration: is regeneration a recapitulation of development?

After damage of the sciatic nerve, a regeneration process is initiated. Neurons in the dorsal root ganglion regrow their axons and functional connections. The molecular mechanisms of this neuronal regenerative process have remained elusive, but a relationship with developmental processes has been conceived. This chapter discusses the applicability of the developmental hypothesis of regeneration to the dorsal root ganglion; this hypothesis states that regeneration of dorsal root ganglion neurons is a recapitulation of development. We present data on changes in gene expression upon sciatic nerve damage, and the expression and function of homeobox genes. This class of transcription factors plays a role in neuronal development. Based on these data, it is concluded that the hypothesis does not hold for dorsal root ganglion neurons, and that regeneration-specific mechanisms exist. Cytokines and the associated Jak/STAT (janus kinase/signal transducer and activator of transcription) signal transduction pathway emerge as constituents of a regeneration-specific mechanism. This mechanism may be the basis of pharmacological strategies to stimulate regeneration

Insulin inhibits extracellular regulated kinase 1/2 phosphorylation in a phosphatidylinositol 3-kinase (PI3) kinase-dependent manner in Neuro2a cells

Insulin signalling is well studied in peripheral tissue, but not in neuronal tissue. To gain more insight into neuronal insulin signalling we examined protein kinase B (PKB) and extracellular regulated kinase 1 and 2 (ERK1/2) regulation in serum-deprived Neuro2a cells. Insulin phosphorylated PKB in a dose-dependent manner but reduced phosphorylation of ERK1/2. Both processes were phosphatidylinositol 3-kinase (PI3K) dependent. Interestingly, blockade of PI3K in combination with insulin induced phosphorylation of ERK1/2. The phosphorylation of ERK1/2 could be blocked with a specific inhibitor of mitogen-activated protein/ERK kinase (MEK), suggesting that it was mediated through the highly conserved RasRafMEKERK1/2 pathway. Prolonged exposure to high concentrations of insulin resulted in a desensitized PI3KPKB route. The insulin-induced inhibition of ERK1/2 phosphorylation was also diminished when the PI3KPKB route was desensitized. Blockade of PI3K in combination with insulin, however, still resulted in an unaltered MEK-dependent phosphorylation of ERK1/2. We conclude that PI3K is an important integrator of insulin signalling in Neuro2a cells as it regulates activation of PKB and inhibition of ERK1/2, and is sensitive to the duration of the insulin stimulus

Age-dependent expression of forkhead box O proteins in the duodenum of rats*

The O subfamily of forkhead box (FoxO) proteins is the downstream effector of the insulin-like growth factor-1/phosphoinositide 3-kinase/protein kinase B (IGF-1/PI3K/PKB) signal pathway. The objective of the present study was to examine the expressions of three members of FoxO proteins, FoxO1, FoxO3a, and FoxO4 in the duodenum of Sprague-Dawley rats at different ages. The result demonstrated that the expression of FoxO4 in rat duodenum showed an age-dependent manner. At Day 21, there were no detectable localization and expression of FoxO4 in the duodenum, while, at Months 2 and 6, localization and expression of FoxO4 were distinct. In addition, FoxO4 staining was primarily concentrated in the cell nuclei of the lamina propria around the intestinal gland of the duodenum in 2-month-old rats, but was not detectable in the same area in 6-month-old rats. Our results showed also that although FoxO3a existed in the cytoplasm of the lamina propria at a low level at the 2- and 6-month marks, it was still not detectable at Day 21. Besides, FoxO1 was not detectable in all parts and stages. Taken together, our findings suggested that the cell-specific and age-dependent expressional patterns of FoxO4 and FoxO3a proteins in the duodenum play some roles in the development and growth performance of the rat duodenum

FoxO4 is the main forkhead transcriptional factor localized in the gastrointestinal tracts of pigs

Forkhead box (Fox) proteins play critical roles in the regulation of differentiation, proliferation, immunity and aging of cells. Most studies on Fox proteins are limited to cultured cells and rodent. The aim of the current study is to detect by immunohistrochemistry whether FoxO1, FoxO3a and FoxO4 proteins are localized in the stomach and intestine of the pig. The results showed that FoxO4 exists in the mucosa in all parts of the stomach and intestine; FoxO3a exists mainly in the lamina propria and muscularis of some parts. However, FoxO1 is not detectable in all parts of the stomach and intestine. Collectively, the results of the present study indicate that there exists a distinct expression pattern of Fox proteins, and that FoxO4 is a primary forkhead transcriptional factor localized in the gastrointestinal tracts of the pig