Involvement of nitric oxide/reactive oxygen species signaling via 8-nitro-cGMP formation in 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells and rat cerebellar granule neurons.

To investigate the role of nitric oxide (NO)/reactive oxygen species (ROS) redox signaling in Parkinson's disease-like neurotoxicity, we used 1-methyl-4-phenylpyridinium (MPP+) treatment (a model of Parkinson's disease). We show that MPP+-induced neurotoxicity was dependent on ROS from neuronal NO synthase (nNOS) in nNOS-expressing PC12 cells (NPC12 cells) and rat cerebellar granule neurons (CGNs). Following MPP+ treatment, we found production of 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), a second messenger in the NO/ROS redox signaling pathway, in NPC12 cells and rat CGNs, that subsequently induced S-guanylation and activation of H-Ras. Additionally, following MPP+ treatment, extracellular signal-related kinase (ERK) phosphorylation was enhanced. Treatment with a mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor attenuated MPP+-induced ERK phosphorylation and neurotoxicity. In conclusion, we demonstrate for the first time that NO/ROS redox signaling via 8-nitro-cGMP is involved in MPP+-induced neurotoxicity and that 8-nitro-cGMP activates H-Ras/ERK signaling. Our results indicate a novel mechanism underlying MPP+-induced neurotoxicity, and therefore contribute novel insights to the mechanisms underlying Parkinson's disease.

Enhancement of Structural fluctuation in the region connecting two kinds of critical points in temperature-pressure-composition three-dimensional phase diagram: Raman studies of benzene/CO2 binary systems up to supercritical region.

Pressure dependence of Raman spectra of benzene/CO2 two-component systems was systematically studied at different temperatures and compositions. We estimated the magnitude of inhomogeneous component in Raman bandwidth to get information on the structural fluctuation in the system. It was found that the inhomogeneous bandwidth attains a maximum on an isothermal plane in the temperature-pressure-composition three-dimensional phase diagram when the state point crosses the line connecting the region where the density fluctuation is large (the vicinity of the critical point of neat CO2) and the region where the concentration fluctuation in a binary system is enhanced (the vicinity of the critical solution point). By accumulating such data, we found that the points of large structural fluctuation comprise a sheet that includes the extension line of the gas-liquid equilibrium line in the phase diagram of neat CO2 and the line connecting critical solution points of the two-component system at different temperatures. Interaction between benzene and CO2 molecules in the supercritical region is briefly discussed.