Nitric oxide show its survival role by NO-PKC pathway through cGMP-dependent or independent on the culture of cerebella granular neurons.

ABSTRACT

The role of nitric oxide in the development of neurons is conflicting. In the present work, cerebellar granule neurons (CGNs) were used as a model to assess the survival role of nitric oxide and to find novel signal transduction pathways related to this role. It is reported that sustained inhibition of nitric oxide production induces apoptosis in differentiated cerebellar granule neurons. The antagonist (MK-801, or ODQ)-induced decrease of cell viability, caspase-3 activated, the expression of P-PKC decreased, which were normalized by the provision of the sodium nitroprusside, an NO donor. The data show that blockade of NO production induces apoptotic death in differentiating CGC through activation of caspase-3. This study provides direct evidence that NO plays an active role in sustaining the survival of developing CGNs and that NO-PKC pathway is important for the survival of CGNs in vitro. The endogenous NO exerts its effects in cGMP-dependent manner while the exogenous NO in cGMP-independent manner.