title: iNOS participates in apoptosis of spinal cord neurons via p-BAD dephosphorylation following ischemia/reperfusion (I/R) injury in rat spinal cord.
abstract: The pro-apoptotic effect of nitric oxide (NO) has been reported both in vivo and in vitro. Previous studies have revealed that NO, especially which produced by inducible nitric oxide synthase (iNOS), has an important effect on apoptosis of neurons in spinal cord ischemia/reperfusion (I/R) injury. To investigate the role of iNOS in this process, a randomized, controlled study was designed using a classical rat model of ischemic spinal cord injury. Fifty-four male Sprague-Dawley rats were randomly divided into three different groups: a sham-operated group (n=6), a vehicle group (I/R, n=24), and an iNOS inhibitor (aminoguanidine: AG) group (I/R+AG, n=24). Rats were sacrificed 6, 12, 24 and 72 h after reperfusion. We examined neurological motor function evaluated by 'Tarlov's score', assessed alterations in the morphology of spinal cord neurons by transmission electron microscopy (TEM), analyzed expression of iNOS at the levels of mRNA and protein, evaluated local concentrations and cellular locations of other key regulatory proteins, and investigated protein-protein interactions. In the vehicle group, iNOS expression, dephosphorylation of p-BAD (Ser 136), disassociation of BAD from p-BAD/14-3-3 dimers, and release of cytochrome c were all increased compared with the sham group. But in the AG group, all the performances above were decreased compared with the vehicle group. Similarly, rats in the sham group got a maximum score of 5 by Tarlov's motor scores evaluation. While the scores were higher in the AG group compared to the vehicle group because iNOS was inhibited. These results indicate that the activity of iNOS plays a critical role in the apoptosis of spinal cord neurons by influencing the dephosphorylation of p-BAD (Ser 136) and the interaction between BAD and 14-3-3.
authors: The First Affiliated Hospital of Nanjing Medical University, Jiangsu 210029, China.
authors: Yiming
authors: Y
authors: Li
authors: Jun
authors: J
authors: Gu
authors: Yuwen
authors: Y
authors: Liu
authors: Hao
authors: H
authors: Long
authors: Guannan
authors: G
authors: Wang
authors: Guoyong
authors: G
authors: Yin
authors: Jin
authors: J
authors: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000378:metabolism* / Q000473:pathology; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: C494821:Bad protein, rat; D051025:bcl-Associated Death Protein; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat