The interaction of Nogo-66 receptor with Nogo-p4 inhibits the neuronal differentiation of neural stem cells

The Nogo-66 receptor (NgR) has been found throughout axons in the adult and maturing CNS. An interaction of Nogo on the oligodendrocyte surface with NgR on axons has been suggested to play an important role in limiting axonal growth. In our study, we found that neural stem cells (NSCs) derived from the spinal cords of rats expressed NgR significantly. After normal NSCs differentiation, the average neuronal neurite length was 97.80+/-6.97 microm and the percentage of differentiated neurons was 34.73+/-5.21% 3 days after the differentiation was initiated in vitro. If NSCs were allowed to differentiate in the presence of Nogo-p4 (the active segment of Nogo-66), the average neurite length and the percentage of differentiated neurons were decreased, respectively, to 60.31+/-6.58 microm and 10.26+/-1.22%. An siRNA-mediated knockdown of NgR on NSCs could reverse the inhibitory effect of Nogo-p4 and restore the average neuronal neurite length as well as the percentage of differentiated neurons to 94.01+/-8.37 microm and 31.84+/-4.03%. These results deepen our knowledge about the distribution of NgR and provide a possible strategy of treating NSCs to ameliorate neuronal differentiation after transplantation.     

Regulation of neurite outgrowth mediated by neuronal calcium sensor-1 and inositol 1,4,5-trisphosphate receptor in nerve growth cones

Calcium acts as an important second messenger in the intracellular signal pathways in a variety of cell functions. Strictly controlled intracellular calcium is required for proper neurite outgrowth of developing neurons. However, the molecular mechanisms of this process are still largely unknown. Neuronal calcium sensor-1 (NCS-1) is a high-affinity and low-capacity calcium binding protein, which is specifically expressed in the nervous system. NCS-1 was distributed throughout the entire region of growth cones located at a distal tip of neurite in cultured chick dorsal root ganglion neurons. In the central domain of the growth cone, however, NCS-1 was distributed in a clustered specific pattern and co-localized with the type 1 inositol 1,4,5-trisphosphate receptor (InsP₃R1). The pharmacological inhibition of InsP₃ receptors decreased the clustered specific distribution of NCS-1 in the growth cones and inhibited neurite outgrowth but did not change the growth cone morphology. The acute and localized loss of NCS-1 function in the growth cone induced by chromophore-assisted laser inactivation (CALI) resulted in the growth arrest of neurites and lamellipodial and filopodial retractions. These findings suggest that NCS-1 is involved in the regulation of both neurite outgrowth and growth cone morphology. In addition, NCS-1 is functionally linked to InsP₃R1, which may play an important role in the regulation of neurite outgrowth.     

Clinicopathological and predictive significance of SIRT1 and peroxisome proliferator-activated receptor gamma in esophageal squamous cell carcinoma: The correlation with EGFR and Survivin

SIRT1 (silent mating type information regulation 2 homolog 1) is an enzyme that deacetylates proteins that contributes to cell survival and angiogenesis. Peroxisome proliferator-activated receptor ? (PPAR ?) is a member of the nuclear steroid hormone receptor superfamily and regulates cell apoptosis and proliferation. The functional roles of SIRT1 and PPAR ? in tumor progression remain controversy. This study aims to investigate the roles of SIRT1 and PPAR ? in esophageal squamous cell carcinoma (ESCC), as well as correlation with expression of EGFR and Survivin. Here, we analyzed the protein expression of SIRT1 and PPAR ? in tumor microarray with ESCC and its associations with clinicopathological parameters and overall survival. Both SIRT1 and PPAR ? were highly expressed in tumor tissues comparing with non-cancerous epithelium. High expression of SIRT1 was positively correlated with advanced TNM stage and poor outcome, while high expression of PPAR ? was positively related with tumor grading, not with patients’ prognosis. In addition, the high expression of SIRT1 was positively correlated with overexpression of EGFR, not related with PPAR ? or Survivin expression status. These data suggests SIRT1 may serve as a predictor of poor prognosis in ESCC, and its mediated tumor-promoting role might be associated with the overexpression of EGFR protein in ESCC.