S-Nitrosoglutathione Mimics the Beneficial Activity of Endothelial Nitric Oxide Synthase-Derived Nitric Oxide in a Mouse Model of Stroke

被引:14
|
作者
Khan, Mushfiquddin [1 ]
Dhammu, Tajinder S. [1 ]
Qiao, Fei [1 ,2 ]
Kumar, Pavan [1 ]
Singh, Avtar K. [2 ,3 ]
Singh, Inderjit [2 ,3 ]
机构
[1] Med Univ South Carolina, Dept Pediat, 513 Childrens Res Inst CRI,173 Ashley Ave, Charleston, SC 29425 USA
[2] Med Univ South Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA
[3] Ralph H Johnson VA Med Ctr, Charleston, SC USA
关键词
S-nitrosoglutathione; eNOS; NO; GSNO; N6022; stroke; neuroprotection; cerebral ischemia; FOCAL CEREBRAL-ISCHEMIA; RAT MODEL; TRIPHENYLTETRAZOLIUM CHLORIDE; REDUCES INFLAMMATION; FUNCTIONAL RECOVERY; ARTERY OCCLUSION; REDUCTASE GSNOR; PROTECTS BRAIN; MECHANISMS; NITROSYLATION;
D O I
10.1016/j.jstrokecerebrovasdis.2019.104470
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: The nitric oxide (NO)-producing activity of endothelial nitric oxide synthase (eNOS) plays a significant role in maintaining endothelial function and protecting against the stroke injury. However, the activity of the eNOS enzyme and the metabolism of major NO metabolite S-nitrosoglutathione (GSNO) are dysregulated after stroke, causing endothelial dysfunction. We investigated whether an administration of exogenous of GSNO or enhancing the level of endogenous GSNO protects against neurovascular injury in wild-type (WI) and eNOS-null (endothelial dysfunction) mouse models of cerebral ischemia-reperfusion (IR). Methods: Transient cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO) for 60 minutes in male adult WT and eNOS null mice. GSNO (0.1 mg/kg body weight, intravenously) or N6022 (GSNO reductase inhibitor, 5.0 mg/kg body weight, intravenously) was administered 30 minutes before MCAO in preinjury and at the reperfusion in postinjury studies. Brain infarctions, edema, and neurobehavioral functions were evaluated at 24 hours after the reperfusion. Results: eNOS-null mice had a higher degree (P < .05) of injury than WT. Pre- or postinjury treatment with either GSNO or N6022 significantly reduced infarct volume, improved neurological and sensorimotor function in both WT and eNOS-null mice. Conclusion: Reduced brain infarctions and edema, and improved neurobehavioral functions by pre- or postinjury GSNO treatment of eNOS knock out mice indicate that GSNO can attenuate IR injury, likely by mimicking the eNOS-derived NO-dependent anti-ischemic and anti-inflammatory functions. Neurovascular protection by GSNO/N6022 in both pre- and postischemic injury groups support GSNO as a promising drug candidate for the prevention and treatment of stroke injury.
引用
收藏
页数:10
相关论文
共 50 条
  • [41] Endothelial Nitric Oxide Synthase Regulates White Matter Changes after Stroke
    Cui, Xu
    Chopp, Michael
    Yan, Tao
    Ning, Ruizhuo
    Roberts, Cynthia
    Zacharek, Alex
    Venkat, Poornima
    Chen, Jieli
    STROKE, 2013, 44 (02)
  • [42] Endothelial nitric oxide synthase plays a main role in producing nitric oxide in the superacute phase of hepatic ischemia prior to the upregulation of inducible nitric oxide synthase
    Miyake, Takashi
    Yokoyama, Yukihiro
    Kokuryo, Toshio
    Mizutani, Tetsushi
    Imamura, Atsushi
    Nagino, Masato
    JOURNAL OF SURGICAL RESEARCH, 2013, 183 (02) : 742 - 751
  • [43] Association of endothelial nitric oxide synthase gene variants with preeclampsia
    Shaheen, Ghazala
    Jahan, Sarwat
    Bibi, Nousheen
    Ullah, Asmat
    Faryal, Rani
    Almajwal, Ali
    Afsar, Tayyaba
    Al-Disi, Dara
    Abulmeaty, Mahmoud
    Al Khuraif, Abdulaziz Abdullah
    Arshad, Mohammed
    Razak, Suhail
    REPRODUCTIVE HEALTH, 2021, 18 (01)
  • [44] Exogenous Nitric Oxide Enhances Disease Resistance by Nitrosylation and Inhibition of S-Nitrosoglutathione Reductase in Peach Fruit
    Yu, Zifei
    Cao, Jixuan
    Zhu, Shuhua
    Zhang, Lili
    Peng, Yong
    Shi, Jingying
    FRONTIERS IN PLANT SCIENCE, 2020, 11
  • [45] Endothelial nitric oxide synthase is not necessary for the early phase of ischemic preconditioning in the mouse
    Guo, Yiru
    Li, Qianhong
    Wu, Wen-Jian
    Tan, Wei
    Zhu, Xiaoping
    Mu, Jingyao
    Bolli, Roberto
    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2008, 44 (03) : 496 - 501
  • [46] Variations of brain endothelial nitric oxide synthase concentration in rat and mouse cortex
    Czambel, R. Kenneth
    Kharlamov, Alexander
    Jones, Stephen C.
    NITRIC OXIDE-BIOLOGY AND CHEMISTRY, 2010, 22 (01): : 51 - 57
  • [47] Coordinated Endothelial Nitric Oxide Synthase Activation by Translocation and Phosphorylation Determines Flow-Induced Nitric Oxide Production in Resistance Vessels
    Figueroa, Xavier F.
    Gonzalez, Daniel R.
    Puebla, Mariela
    Acevedo, Juan P.
    Rojas-Libano, Daniel
    Duran, Walter N.
    Boric, Mauricio P.
    JOURNAL OF VASCULAR RESEARCH, 2013, 50 (06) : 498 - 511
  • [48] Local nitric oxide synthase activity in a model of neuropathic pain
    Levy, D
    Zochodne, DW
    EUROPEAN JOURNAL OF NEUROSCIENCE, 1998, 10 (05) : 1846 - 1855
  • [49] Modulation by S-nitrosoglutathione (a natural nitric oxide donor) of photosystem in Pisum sativum leaves, as revealed by chlorophyll fluorescence: Light-dependent aggravation of nitric oxide effects
    Saini, Deepak
    Bapatla, Ramesh B.
    Pandey, Jayendra
    Aswani, Vetcha
    Sunil, Bobba
    Gahir, Shashibhushan
    Bharath, Pulimamidi
    Subramanyam, Rajagopal
    Raghavendra, Agepati S.
    PLANT SCIENCE TODAY, 2023, 10 (02): : 393 - 398
  • [50] Expression of endothelial nitric oxide synthase in the ischemic penumbra: relationship to expression of neuronal nitric oxide synthase and vascular endothelial growth factor
    Leker, RR
    Teichner, A
    Ovadia, H
    Keshet, E
    Reinherz, E
    Ben-Hur, T
    BRAIN RESEARCH, 2001, 909 (1-2) : 1 - 7