No abstract

Cell division cycle protein 37 (Cdc37), a molecular chaperone takes part in a series of cellular processes including cell signal transduction, cell cycle progression, cell proliferation, cell motility, oncogenesis and malignant progression. It can not only recruit immature protein kinases to HSP90 but also work alone. Cdc37 was reported to be associated with neurogenesis, neurite outgrowth, axon guidance and myelination. However, the roles of Cdc37 on Schwann cells (SC) after peripheral nerve injury (PNI) remain unknown. In this study, we found that the expression of Cdc37 increased and reached the peak at 1 week after sciatic nerve crush (SNC), which was consistent with that of proliferation cell nuclear antigen. Immunofluorescence verified that Cdc37 co-localized with SC in vivo and in vitro. Intriguingly, Cdc37 protein level was potentiated in the model of TNF-α-induced SC proliferation. Moreover, we found that Cdc37 silencing impaired proliferation of SC in vitro. Moreover, Cdc37 suppression attenuated kinase signaling pathways of Raf-ERK and PI3K/AKT which are crucial cell signaling for SC proliferation. Finally, we found that Cdc37 silencing inhibited SC migration in vitro. In conclusion, we demonstrated that the way Cdc37 contributed to SC proliferation is likely via activating kinase signaling pathways of Raf-ERK and PI3K/AKT, and CDC37 was also involved in SC migration after SNC.

Objective SSTR2 is a member of superfamily of SST receptor (SSTR), and widely expressed in the brain; however, the knowledge of its functions in area adjacent to hematoma after intracerebral hemorrhage (ICH) is still limited. Method The role of SSTR2 in the processes of ICH was explored by conducting an ICH rat model. Western blot and immunohistochemistry were employed to examine the level of SSTR2 in area adjacent to hematoma after ICH. Immunofluorescent staining was used to observe the spatial correlation of SSTR2 with cellular types adjacent to hematoma after ICH. RNA interference specific to SSTR2 was adopted in PC12 cells to clarify the causal correlation between SSTR2 and neuronal activities. Results Increased expression of SSTR2 was observed and restricted to the neurons adjacent to hematoma following ICH. Immunofluorescent staining showed that SSTR2 was significant increased in neurons, but not astrocytes or microglia. Increasing SSTR2 level was found to be accompanied by the up-regulation of activated caspase-3 and the down-expression of p-Akt in a time-dependent manner. What's more, using SSTR2 RNA interference (SSTR2-RNAi) in PC12 cells, we indicated that SSTR2 might have a pro-apoptotic role in neurons. Conclusion We speculated that SSTR2 might exert its pro-apoptotic function in neurons through inhibiting Akt activity following ICH.