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Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia-Reperfusion Injury.
Anat Rec (Hoboken). 2016 Feb; 299(2):246-55.AR

Abstract

Inducible nitric oxide synthase (iNOS) is a key enzyme in regulating nitric oxide (NO) synthesis under stress, and NO has varying ability to regulate apoptosis. The aim of this study was to investigate the effects and possible mechanism of action of iNOS on neuronal apoptosis in a rat model of cerebral focal ischemia and reperfusion injury in rats treated with S-methylisothiourea sulfate (SMT), a high-selective inhibitor of iNOS. Seventy-two male Sprague-Dawley (SD) rats were randomly divided into three groups: the sham, middle cerebral artery occlusion (MCAO) + vehicle, and MCAO + SMT groups. Neurobehavioral deficits, infarct zone size, and cortical neuron morphology were evaluated through the modified Garcia scores, 2,3,5-triphenyltetrazolium chloride (TTC), and Nissl staining, respectively. Brain tissues and serum samples were collected at 72 hr post-reperfusion for immunohistochemical analysis, Western blotting, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin Nick End Labeling assay (TUNEL) staining, and enzyme assays. The study found that inhibition of iNOS significantly attenuated the severity of the pathological changes observed as a result of ischemia-reperfusion injury: SMT reduced NO content as well as total nitric oxide synthase (tNOS) and iNOS activities in both ischemic cerebral hemisphere and serum, improved neurobehavioral scores, reduced mortality, reduced the infarct volume ratio, attenuated morphological changes in cortical neurons, decreased the rate of apoptosis (TUNEL and caspase-3-positive), and increased phospho (p)-AKT expression in ischemic penumbra. These results suggested that inhibition of iNOS might reduce the severity of ischemia-reperfusion injury by inhibiting neuronal apoptosis via maintaining p-AKT activity.

Authors+Show Affiliations

Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.Department of Neurology, the Center Hospital of China Natural Petroleum Corporation, Lang Fang, 065000, China.Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26598930

Citation

Zheng, Li, et al. "Effects and Mechanism of Action of Inducible Nitric Oxide Synthase On Apoptosis in a Rat Model of Cerebral Ischemia-Reperfusion Injury." Anatomical Record (Hoboken, N.J. : 2007), vol. 299, no. 2, 2016, pp. 246-55.
Zheng L, Ding J, Wang J, et al. Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia-Reperfusion Injury. Anat Rec (Hoboken). 2016;299(2):246-55.
Zheng, L., Ding, J., Wang, J., Zhou, C., & Zhang, W. (2016). Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia-Reperfusion Injury. Anatomical Record (Hoboken, N.J. : 2007), 299(2), 246-55. https://doi.org/10.1002/ar.23295
Zheng L, et al. Effects and Mechanism of Action of Inducible Nitric Oxide Synthase On Apoptosis in a Rat Model of Cerebral Ischemia-Reperfusion Injury. Anat Rec (Hoboken). 2016;299(2):246-55. PubMed PMID: 26598930.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia-Reperfusion Injury. AU - Zheng,Li, AU - Ding,Junli, AU - Wang,Jianwei, AU - Zhou,Changman, AU - Zhang,Weiguang, Y1 - 2015/12/29/ PY - 2015/02/16/received PY - 2015/09/21/revised PY - 2015/10/08/accepted PY - 2015/11/25/entrez PY - 2015/11/26/pubmed PY - 2016/10/16/medline KW - apoptosis KW - cerebral ischemia and reperfusion injury KW - inducible nitric oxide synthase KW - p-AKT SP - 246 EP - 55 JF - Anatomical record (Hoboken, N.J. : 2007) JO - Anat Rec (Hoboken) VL - 299 IS - 2 N2 - Inducible nitric oxide synthase (iNOS) is a key enzyme in regulating nitric oxide (NO) synthesis under stress, and NO has varying ability to regulate apoptosis. The aim of this study was to investigate the effects and possible mechanism of action of iNOS on neuronal apoptosis in a rat model of cerebral focal ischemia and reperfusion injury in rats treated with S-methylisothiourea sulfate (SMT), a high-selective inhibitor of iNOS. Seventy-two male Sprague-Dawley (SD) rats were randomly divided into three groups: the sham, middle cerebral artery occlusion (MCAO) + vehicle, and MCAO + SMT groups. Neurobehavioral deficits, infarct zone size, and cortical neuron morphology were evaluated through the modified Garcia scores, 2,3,5-triphenyltetrazolium chloride (TTC), and Nissl staining, respectively. Brain tissues and serum samples were collected at 72 hr post-reperfusion for immunohistochemical analysis, Western blotting, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin Nick End Labeling assay (TUNEL) staining, and enzyme assays. The study found that inhibition of iNOS significantly attenuated the severity of the pathological changes observed as a result of ischemia-reperfusion injury: SMT reduced NO content as well as total nitric oxide synthase (tNOS) and iNOS activities in both ischemic cerebral hemisphere and serum, improved neurobehavioral scores, reduced mortality, reduced the infarct volume ratio, attenuated morphological changes in cortical neurons, decreased the rate of apoptosis (TUNEL and caspase-3-positive), and increased phospho (p)-AKT expression in ischemic penumbra. These results suggested that inhibition of iNOS might reduce the severity of ischemia-reperfusion injury by inhibiting neuronal apoptosis via maintaining p-AKT activity. SN - 1932-8494 UR - https://www.unboundmedicine.com/medline/citation/26598930/Effects_and_Mechanism_of_Action_of_Inducible_Nitric_Oxide_Synthase_on_Apoptosis_in_a_Rat_Model_of_Cerebral_Ischemia_Reperfusion_Injury_ L2 - https://doi.org/10.1002/ar.23295 DB - PRIME DP - Unbound Medicine ER -