Involvement of peroxynitrite and hydroxyradical generated from nitric oxide in hypoxia/reoxygenation injury in rat cerebrocortical slices

Oka, Michiko; Hirouchi, Masaaki; Itoh, Yoshinori; Ukai, Yojiro

doi:10.1016/s0028-3908(99)00197-5

Cited by 28 publications

(10 citation statements)

References 47 publications

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“…Because hypoxic injury can enhance the expression of EPO in neurons (Bernaudin et al, 2000), we elected to examine the protective capacity of EPO against two distinct insults that were linked intimately. Our present work illustrates that NO is a downstream mediator of anoxic injury in hippocampal neurons consistent with prior studies (Erdemli and Crunelli, 2000;Oka et al, 2000;Lin and Maiese, 2001). Inhibition of iNOS activity significantly increases neuronal viability during anoxia, suggesting that NO generation through NOS is cytotoxic to neurons.…”

Section: Discussionsupporting

confidence: 92%

Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8

Chong

Lin

Kang

et al. 2002

J of Neuroscience Research

147

156

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Erythropoietin (EPO) modulates primarily the proliferation of immature erythroid precursors, but little is known of the potential protective mechanisms of EPO in the central nervous system. We therefore examined the ability of EPO to modulate a series of death-related cellular pathways during anoxia and free radical induced neuronal degeneration. Neuronal injury was evaluated by trypan blue, DNA fragmentation, membrane phosphatidylserine exposure, protein kinase B phosphorylation, cysteine protease activity, mitochondrial membrane potential, and mitogen-activated protein (MAP) kinase phosphorylation. We demonstrate that constitutive neuronal EPO is insufficient to prevent cellular injury, but that signaling through the EPO receptor remains biologically responsive to exogenous EPO administration. Exogenous EPO is both necessary and sufficient to prevent acute genomic DNA destruction and subsequent phagocytosis through membrane PS exposure, because neuronal protection by EPO is completely abolished by co-treatment with an anti-EPO neutralizing antibody. Through pathways that involve the initial activation of protein kinase B, EPO maintains mitochondrial membrane potential. Subsequently, EPO inhibits caspase 8-, caspase 1-, and caspase 3-like activities linked to cytochrome c release through mechanisms that are independent from the MAP kinase systems of p38 and JNK. Elucidating some of the novel neuroprotective pathways employed by EPO may further the development of new therapeutic strategies for neurodegenerative disorders.

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Section: Discussionsupporting

confidence: 92%

Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8

Chong

Lin

Kang

et al. 2002

J of Neuroscience Research

147

156

View full text Add to dashboard Cite

show abstract

“…tective (Huang et al, 1994(Huang et al, , 1996. We also reported in rat cerebrocortical slices that NO formed by the activation of Na ϩ as well as Ca 2ϩ channels during exposure to hypoxia/glucose deprivation is implicated in the etiology of ischemic cerebral damage, in which NO is converted to the toxic radical peroxynitrite and leads to a cell death (Oka et al, 2000a). Anoxic injury of cultured astrocytes was reported to be partly dependent on Ca 2ϩ influx via L-type voltage-gated Ca 2ϩ channels (Huan et al, 1992).…”

Section: Discussionmentioning

confidence: 93%

Functional expression of constitutive nitric oxide synthases regulated by voltage‐gated Na⁺ and Ca²⁺ channels in cultured human astrocytes

Oka

Wada

Yamamoto

et al. 2004

Glia

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We report the functional characterization of constitutive nitric oxide synthase(s) (NOS) such as neuronal and endothelial NOS in cultured human astrocytes. Exposure of cultured human astrocytes to 1 microM veratridine or 50 mM KCl produced a pronounced increase in a calmodulin-dependent NOS activity estimated from cGMP formation. The functional expression of voltage-gated Na(+) channel, which is estimated by the response to veratridine, appeared to be earlier (at second day in culture) than that of voltage-gated Ca(2+) channels, which are estimated by the response to the KCl stimulation (at fourth day in culture). The KCl-evoked NO synthesis was totally reversed by L-type Ca(2+) channel blockers such as nifedipine and verapamil, but not by omega-conotoxin GVIA, an N-type Ca(2+) channel blocker, or omega-agatoxin IVA, a P/Q-type Ca(2+) channel blocker. In addition, verapamil abolished the KCl-induced increase in the intracellular free Ca(2+) concentration. RT-PCR analysis revealed that mRNA for neuronal and endothelial NOS was expressed in human astrocytes. In addition, Western blot analysis and double labeling of NOS and glial fibrillary acidic protein (GFAP) showed that cultured human astrocytes expressed neuronal NOS and endothelial NOS as well as the alpha(1) subunit of Ca(2+) channel. These results suggest that human astrocytes express constitutive NOS that are regulated by voltage-gated L-type Ca(2+) channel as well as Na(+) channel.

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“…Interestingly, it has been found that premature apoptosis of pericytes and endothelial cells can be induced by poly(ADP-ribosyl)ation [121,122] which is in turn caused by OH ؒ and ONOO - [123] . The presence of apoptotic bodies along with chromatin fragmentation in cells of the retinal vessels have been demonstrated [124] .…”

Section: Diabetic Retinopathymentioning

confidence: 99%

Free Radicals, Antioxidants and Diabetes: Embryopathy, Retinopathy, Neuropathy, Nephropathy and Cardiovascular Complications

et al. 2006

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The metabolic disturbances in the insulin-dependent diabetes mellitus or type 1 and noninsulin-dependent diabetes mellitus or type 2 are associated with a number of complications including cardiovascular diseases, nephropathy, neuropathy, retinopathy leading to blindness and embryopathy or congenital malformations. Maternal diabetes is associated with a high incidence of congenital malformations and fetal abortions. Heart and kidney anomalies, along with central nervous system defects are frequent manifestations of a maternal diabetic environment. Glycation products from excess glucose can chemically modify DNA causing mutations and complex DNA rearrangements. Therefore, DNA damage in fetal tissues as a result of maternal diabetes may reflect a level of genomic injury sufficient to affect embryonic development. The formation of advanced glycation end products can accelerate vascular occlusion by quenching the vasodilating agent nitric oxide. Interaction with high-affinity receptors located on monocytes and macrophages can enhance the production of free radicals and reactive oxygen/nitrogen species, the secretion of tumor necrosis factor-α, interleukin-1 and insulin-like growth factor 1 which can proliferate endothelial, mesangial and smooth muscle cells and hence contribute significantly to the pathogenesis of cardiovascular complications. Retinopathy is characterized by increased vascular permeability, by vascular closure, together with the growth of new blood vessels on the retina and posterior surface of the vitreous. Reactive oxygen species are involved in decreased retinal blood flow, increased vascular permeability and disruption of blood-retinal barrier. The involvement of oxidative stress in the pathology of diabetes from its associated cardiovascular dysfunctions, nephropathy, neuropathy, retinopathy (leading to blindness) and embryopathy or congenital malformations, suggests that potential management of diabetes could benefit from use of dietary biofactors in medicinal and food plants. There is therefore a requirement for research to focus on the molecular mechanisms of action of extracts and/or the biofactors flavonoids, proanthocyanidins, alkaloids, etc. derived from these plants.

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Involvement of peroxynitrite and hydroxyradical generated from nitric oxide in hypoxia/reoxygenation injury in rat cerebrocortical slices

Cited by 28 publications

References 47 publications

Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8

Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8

Functional expression of constitutive nitric oxide synthases regulated by voltage‐gated Na⁺ and Ca²⁺ channels in cultured human astrocytes

Free Radicals, Antioxidants and Diabetes: Embryopathy, Retinopathy, Neuropathy, Nephropathy and Cardiovascular Complications

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Involvement of peroxynitrite and hydroxyradical generated from nitric oxide in hypoxia/reoxygenation injury in rat cerebrocortical slices

Cited by 28 publications

References 47 publications

Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8

Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8

Functional expression of constitutive nitric oxide synthases regulated by voltage‐gated Na+ and Ca2+ channels in cultured human astrocytes

Free Radicals, Antioxidants and Diabetes: Embryopathy, Retinopathy, Neuropathy, Nephropathy and Cardiovascular Complications

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Functional expression of constitutive nitric oxide synthases regulated by voltage‐gated Na⁺ and Ca²⁺ channels in cultured human astrocytes