Cyclooxygenase-2 Does Not Contribute to Postischemic Production of Reactive Oxygen Species

Kunz, Alexander; Anrather, Josef; Zhou, Ping; Orio, Marcello; Iadecola, Costantino

doi:10.1038/sj.jcbfm.9600369

Cited by 85 publications

(86 citation statements)

References 48 publications

(100 reference statements)

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“…Procedures for MCA occlusion have been published previously (Park et al, 2004;Cho et al, 2005a;Kunz et al, 2007) and are only summarized here. Mice were anesthetized with a mixture of isoflurane (1.5-2%), oxygen, and nitrogen.…”

Section: Mca Occlusion and Measurement Of Ischemic Cerebral Blood Flowmentioning

confidence: 99%

“…Brain sections were collected at 600 m intervals and stained with thionine. Infarct volume was determined using an image analyzer (MCID; Imaging Research, St. Catharines, Ontario, Canada) (Cho et al, 2005a;Kunz et al, 2007). To eliminate the contribution of postischemic edema to the volume of injury, values were corrected for swelling according to the method of Lin et al (1993) as described previously .…”

Section: Infarct Volume Measurementmentioning

confidence: 99%

“…Procedures for quantification of the fluorescence signal have been described previously (Cho et al, 2005a;Girouard et al, 2007;Kunz et al, 2007). Sections were analyzed with a Nikon (Melville, NY) E800 fluorescence microscope equipped with filter sets (Chroma Technology, Rockingham, VT) customized for detection of hydroethidine oxidation products (for ROS production) or FITC (for 3-NT immunoreactivity).…”

Section: Quantification Of Ros Production and 3-nitrotyrosine Immunormentioning

confidence: 99%

“…ROS production was determined using in vivo hydroethidine microfluorography (Kondo et al, 1997), as described previously (Cho et al, 2005a;Kunz et al, 2007). Hydroethidine is a cell-permeant dye that is oxidized to ethidium and related products by superoxide (Robinson et al, 2006).…”

Section: Quantification Of Ros Production and 3-nitrotyrosine Immunormentioning

confidence: 99%

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Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

Kunz¹,

Park²,

Abe³

et al. 2007

J. Neurosci.

132

117

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Cerebral ischemic preconditioning or tolerance is a powerful neuroprotective phenomenon by which a sublethal injurious stimulus renders the brain resistant to a subsequent damaging ischemic insult. We used lipopolysaccharide (LPS) as a preconditioning stimulus in a mouse model of middle cerebral artery occlusion (MCAO) to examine whether improvements in cerebrovascular function contribute to the protective effect. Administration of LPS 24 h before MCAO reduced the infarct by 68% and improved ischemic cerebral blood flow (CBF) by 114% in brain areas spared from infarction. In addition, LPS prevented the dysfunction in cerebrovascular regulation induced by MCAO, as demonstrated by normalization of the increase in CBF produced by neural activity, hypercapnia, or by the endotheliumdependent vasodilator acetylcholine. These beneficial effects of LPS were not observed in mice lacking inducible nitric oxide synthase (iNOS) or the nox2 subunit of the superoxide-producing enzyme NADPH oxidase. LPS increased reactive oxygen species and the peroxynitrite marker 3-nitrotyrosine in wild-type mice but not in nox2 nulls. The peroxynitrite decomposition catalyst 5,10,15, 20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) attenuated LPS-induced nitration and counteracted the beneficial effects of LPS on infarct volume, ischemic CBF, and vascular reactivity. Thus, LPS preserves neurovascular function and ameliorates CBF in regions of the ischemic territory at risk for infarction. This effect is mediated by peroxynitrite formed from iNOS-derived NO and nox2-derived superoxide. The data indicate that preservation of cerebrovascular function is an essential component of ischemic tolerance and suggest that combining neuroprotection and vasoprotection may be a valuable strategy for treating ischemic brain injury.

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Section: Mca Occlusion and Measurement Of Ischemic Cerebral Blood Flowmentioning

confidence: 99%

Section: Infarct Volume Measurementmentioning

confidence: 99%

Section: Quantification Of Ros Production and 3-nitrotyrosine Immunormentioning

confidence: 99%

Section: Quantification Of Ros Production and 3-nitrotyrosine Immunormentioning

confidence: 99%

See 2 more Smart Citations

Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

Kunz¹,

Park²,

Abe³

et al. 2007

J. Neurosci.

132

117

View full text Add to dashboard Cite

show abstract

“…PGs are produced as a result of cyclooxygenase (COX) activity and modulate cerebral blood flow regulation, synaptic transmission, neurotrophin production, angiogenesis, gene expression and can change such biological processes like pain perception, body temperature and sleep/awake cycle (Ahmadi et al, 2002;Kunz et al, 2006;Urade and Hayashi, 1999;Toyomoto et al, 2004;Chen et al, 2002;Chen and Bazan, 2005;Zhu et al, 2006). In addition, many studies have attested to the importance of brain PGs in the development of Alzheimer's disease, stroke, brain inflammation, traumatic brain injury and neurodegenerative diseases Bazan et al, 1995;Minghetti, 2004).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin transporter expression in mouse brain during development and in response to hypoxia

et al. 2007

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Prostaglandins (PGs) are bioactive lipid mediators released following brain hypoxic-ischemic injury. Clearance and re-uptake of these prostaglandins occur via a transmembrane prostaglandin transporter (PGT), which exchanges PG for lactate. We used western blot analyses to examine the PGT developmental profile and its regional distribution as well as changes in transporter expression during chronic hypoxia. Microsomal preparations from four brain regions (cortex, hippocampus, cerebellum and brainstem/diencephalon) showed gradual increases in prostaglandin transporter expression in all brain regions examined from postnatal day 1 till day 30. There was a significant regional heterogeneity in the prostaglandin transporter expression with highest expression in the cortex, followed by cerebellum and hippocampus, and least expressed in the brainstem-diencephalon. To further delineate the pattern of prostaglandin transporter expression, separate astrocytic and neuronal microsomal preparations were also examined. In contrast to neurons, which had a robust expression of prostaglandin transporters, astrocytes had very little PGT expression under basal conditions. In response to chronic hypoxia, there was a significant decline in PGT expression in vivo and in neurons in vitro, whereas cultured astrocytes increased their PGT expression. This is the first report on PGT expression in the central nervous system (CNS) and our studies suggest that PGTs have 1) a widespread distribution in the CNS; 2) a gradual increase and a differential expression in various regions during brain development; and 3) striking contrast in expression between glia and neurons, especially in response to hypoxia. Since PGTs play a role as prostaglandin-lactate exchangers, we hypothesize that PGTs are important in the CNS during stress such as hypoxia.

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Ginkgo biloba active compounds can modulate the development of acute mountain sickness and ischemic stroke as discovered by network pharmacology and molecular docking

Guo,

Kang,

et al. 2024

iLABMED

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BackgroundA combination of molecular docking, molecular dynamics simulations, and herbal network pharmacology was used to investigate the shared key targets and potential mechanisms underlying the preventive effects of Ginkgo biloba active compounds against acute mountain sickness (AMS) and ischemic stroke (IS).Material and MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to screen the main active compounds of Ginkgo biloba and their corresponding targets. We obtained AMS‐related genes by mining several databases and cross‐correlated them with key active compounds of Ginkgo biloba to identify relevant action targets for treating AMS. The STRING database was used to construct a protein–protein interaction network of the effect of Ginkgo biloba active compounds on AMS targets. The expression of genes in the network was analyzed in an IS dataset to identify common key targets of Ginkgo biloba active compounds for both AMS and IS prevention.ResultsThe intersection between the targets of Ginkgo biloba active compounds and AMS‐related genes identified 43 overlapping genes. Analysis of the protein–protein interaction network showed that VEGFA, TP53, SERPINE1, and PTGS2 were among the key hub genes. Analysis of the IS dataset identified significant differences in the expression levels of CAT, TP53, CXCL8, NFKBIA, and PTGS2. These genes were used to construct a visual nomogram prediction model for IS prognosis with promising clinical implications. Molecular docking and molecular dynamics simulations indicated that sesamin stably targeted and bound to PTGS2.ConclusionsActive ingredients of Ginkgo biloba, including luteolin, quercetin, and sesamin, have the potential to modulate the development of AMS and IS through targeted interactions with key proteins, including TP53, CXCL8, NFKBIA, PTGS2, and CAT.

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Cyclooxygenase-2 Does Not Contribute to Postischemic Production of Reactive Oxygen Species

Cited by 85 publications

References 48 publications

Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

Prostaglandin transporter expression in mouse brain during development and in response to hypoxia

Ginkgo biloba active compounds can modulate the development of acute mountain sickness and ischemic stroke as discovered by network pharmacology and molecular docking

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