Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications
| Autor: | Sana Iqbal, J. Marc Simard, Volodymyr Gerzanich, Caron M. Hong, Erik G. Hayman, David B. Kurland, Jesse A. Stokum |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Gene isoform
Pathology medicine.medical_specialty lcsh:Diseases of the circulatory (Cardiovascular) system Subarachnoid hemorrhage lcsh:Medical technology subarachnoid hemorrhage (SAH) Bioinformatics Article Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation medicine cardiovascular diseases Pathological nitric oxide (NO) 030304 developmental biology 0303 health sciences biology business.industry Heparin General Medicine medicine.disease Pathophysiology 3. Good health nervous system diseases Nitric oxide synthase NOS-2 NOS-3 chemistry NOS-1 lcsh:R855-855.5 lcsh:RC666-701 biology.protein business 030217 neurology & neurosurgery Peroxynitrite |
| Zdroj: | Brain Circulation, Vol 2, Iss 1, Pp 8-19 (2016) |
| ISSN: | 2455-4626 |
| Popis: | Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH. We examine the effects of SAH on the function of the various NOS isoforms, with a particular focus on the pathological effects of NOS-2 and on the mechanisms responsible for its transcriptional upregulation. Finally, we review interventions to block NOS-2 upregulation or to counteract its effects, with an emphasis on the potential therapeutic strategies to improve outcomes in patients afflicted with SAH. There is still much to be learned regarding the apparently maladaptive response of NOS-2 and its harmful product NO in SAH. However, the available evidence points to crucial effects that, on balance, are adverse, making the NOS-2/NO/peroxynitrite axis an attractive therapeutic target in SAH. |
| Databáze: | OpenAIRE |
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