Cyclosporin-A inhibits constitutive nitric oxide synthase activity and neuronal and endothelial nitric oxide synthase expressions after spinal cord injury in rats.
Nitric oxide (NO) plays a role in the pathophysiology of spinal cord injury (SCI). NO is produced by three types of nitric oxide synthase (NOS) enzymes: The constitutive Ca2+/calmodulin-dependent neuronal NOS (nNOS) and endothelial NOS (eNOS) isoforms, and the inducible calcium-independent isoform (iNOS). During the early stages of SCI, nNOS and eNOS produce significant amounts of NO, therefore, the regulation of their activity and expression may participate in the damage after SCI. In the present study, we used Cyclosporin-A (CsA) to further substantiate the role of Ca-dependent NOS in neural responses associated to SCI. Female Wistar rats were subjected to SCI by contusion, and killed 4 h after lesion. Results showed an increase in the activity of constitutive NOS (cNOS) after lesion, inhibited by CsA (2.5 mg/kg i.p.). Western blot assays showed an increased expression of both nNOS and eNOS after trauma, also antagonized by CsA administration.
Diaz-Ruiz
Araceli
A
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez, S.S.A., México.
Vergara
Paula
P
Perez-Severiano
Francisca
F
Segovia
Jose
J
Guizar-Sahagún
Gabriel
G
Ibarra
Antonio
A
Ríos
Camilo
C
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000201:enzymology*
D000199:Actins; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D009419:Nerve Tissue Proteins; D016572:Cyclosporine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat