Spatiotemporal patterns of dexamethasone-induced Ras protein 1 expression in the central nervous system of rats with experimental autoimmune encephalomyelitis.
Dexamethasone-induced Ras protein 1 (Dexras 1), a brain-enriched member of Ras subfamily of guanosine triphosphatases, as a novel physiologic nitric oxide (NO) effector, anchor neuronal nitric oxide synthase (nNOS) that could form a ternary complex with carboxy-terminal PDZ ligand of nNOS (CAPON) and nNOS, to specific targets to enhance NO signaling. The present study was to explore the expression pattern of Dexras 1 in the development of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Western blot and immunochemistry analysis showed that the gene and protein expression of Dexras 1 in the central nervous system (CNS) of rats increased significantly during the process of EAE compared with control groups (p < 0.01) and maintain a high level in the remission period. The protein expressions of nNOS and CAPON in hippocampus were approximately paralleled Dexras 1. Immunofluorescence revealed that both neurons and glial cells expressed the Dexras 1 in EAE CNS. Importantly, the damaged CNS in EAE-affected rats showed the codistribution between Dexras 1 and caspase 3, indicating the role of Dexras 1 played in the apoptotic process in EAE. Furthermore, colocalizations of Dexras 1 were observed in neurons and glial cells in CNS with nNOS or CAPON, supporting the ternary complex in this model. Thus, these findings suggest the postulation that Dexras 1 might participate into CNS neuronal cell death and demyelination in the whole process of EAE through regulating the NO signaling by binding to nNOS and CAPON.
Gao
Heng
H
The Affiliated Jiangyin Hospital of Nantong University, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
Gao
Ying
Y
Li
Xiaohong
X
Shen
Aiguo
A
Yan
Meijuan
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C488082:NOS1AP protein, rat; C528215:Rasd1 protein, rat; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D018631:ras Proteins