Alterations in the time course of expression of the Nox family in the brain in a rat experimental cerebral ischemia and reperfusion model: effects of melatonin

Li, Haiying; Wang, Yang; Feng, Dongxia; Liu, Zhenying; Xu, Min; Gao, Anju; Tian, Fengxuan; Zhang, Li; Cui, Yunan; Wang, Zhong

doi:10.1111/jpi.12148

Cited by 74 publications

(54 citation statements)

References 35 publications

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“…As described previously [32], we costained brain sections for CBS and NeuN or MST and NeuN to evaluate the expressions of CBS and 3MST in neurons. All the primary antibodies were applied at dilution of 1:100, and all the second antibodies were diluted at 1:500.…”

Section: Immunofluorescence Microscopymentioning

confidence: 99%

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Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats

Cui

Duan

et al. 2015

Mol Neurobiol

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Background: Hydrogen sulfide (H 2 S) has shown a neuroprotective role in several cerebrovascular diseases. This study aimed to explore the underlying mechanisms of H 2 S in early brain injury after subarachnoid hemorrhage (SAH). Methods: One hundred seventy-seven male Sprague-Dawley rats were employed in this study. Sodium hydrosulfide (NaHS), a donor of H 2 S, was injected intraperitoneally at 60 min after SAH was induced by endovascular perforation. Western blot analysis determined the expression of several proteins of interest, and an immunofluorescence assay was used to examine neuronal apoptosis. Results: Exogenous NaHS markedly improved neurological scores, attenuated brain edema, and ameliorated neuronal apoptosis at 24 h after SAH induction. The underlying mechanisms of H 2 S in ameliorating neuronal apoptosis might be executed through inhibition of the activity of mammalian sterile 20-like kinase 1 (MST1) protein. Western blot analysis demonstrated that exogenous NaHS decreased cleaved MST1 (cl-MST1) while increasing full-length MST1 expression. This anti-apoptotic effect of H 2 S could be reversed by chelerythrine, which could activate MST1 via caspase-dependent cleavage. Conclusions: Exogenous NaHS, as a donor of H 2 S, could ameliorate early brain injury after SAH by inhibiting neuronal apoptosis by reducing the activity of the MST1 protein.

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Section: Immunofluorescence Microscopymentioning

confidence: 99%

“…Normal rabbit IgG was used as a negative control (data not shown). The fluorescence images were captured, and the relative fluorescence intensity was analyzed as described in our previous study [32].…”

Section: Immunofluorescence Microscopymentioning

confidence: 99%

Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats

Cui

Duan

et al. 2015

Mol Neurobiol

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“…Additional studies revealed that NOX2 is primarily localized in neurons and endothelial cells at early time-points (3–6 h) after tGCI, followed by expression in microglial cells at later time-points (72 hr) [132, 134]. Likewise, studies in focal cerebral ischemia animal models also found that NOX2 and NOX4 mRNA and protein, as well as NOX activity are elevated in the peri-infarct region of the cerebral cortex from 2–48 h after reperfusion [135–138]. Few studies have examined later time-points, but one study found NOX2 protein expression was markedly elevated in the peri-infarct region of the cortex up to 2 weeks after focal cerebral ischemia [139].…”

Section: Introductionmentioning

confidence: 99%

NADPH oxidase in brain injury and neurodegenerative disorders

Merry

Wang

Zhang

et al. 2017

Mol Neurodegeneration

341

309

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Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology. NADPH oxidase has the primary function to generate free radicals. In particular, there is growing evidence that the isoforms NOX1, NOX2, and NOX4 can be upregulated by a variety of neurodegenerative factors. The majority of recent studies have shown that genetic and pharmacological inhibition of NADPH oxidase enzymes are neuroprotective and able to reduce detrimental aspects of pathology following ischemic and traumatic brain injury, as well as in chronic neurodegenerative disorders. This review aims to summarize evidence supporting the role of NADPH oxidase in the pathology of these neurological disorders, explores pharmacological strategies of targeting this major oxidative stress pathway, and outlines obstacles that need to be overcome for successful translation of these therapies to the clinic.

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“…34 Unexpectedly, the upregulation of Nox4 was gradually induced and reached maximal levels at day 4 after brain ischemia, and was higher in pMCAO than in tMCAO (Figures 1b and c). Although there is a paper demonstrating the immediate upregulation of Nox4 after brain ischemia, 35 some papers have shown that Nox4 is significantly upregulated at 24 hours after MCAO in mice [36][37][38] . In particular, Kleinschnitz et al 36 demonstrated the significant upregulation of Nox4 in the cortex at later than 24 hours after brain ischemia.…”

Section: Brain Pericytes Express Nox4mentioning

confidence: 99%

Detrimental role of pericyte Nox4 in the acute phase of brain ischemia

Nishimura

Ago

Kuroda

et al. 2015

J Cereb Blood Flow Metab

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Pericytes are mural cells abundantly present in cerebral microvessels and play important roles, including the formation and maintenance of the blood-brain barrier. Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly under pathological conditions. In the present study, we found that the expression of Nox4 was markedly induced in microvascular cells, including pericytes, in peri-infarct areas after middle cerebral artery occlusion stroke models in mice. The upregulation of Nox4 was greater in a permanent middle cerebral artery occlusion model compared with an ischemia/reperfusion transient middle cerebral artery occlusion model. We performed permanent middle cerebral artery occlusion on mice with Nox4 overexpression in pericytes (Tg-Nox4). Infarct volume was significantly greater with enhanced reactive oxygen species production and blood-brain barrier breakdown in peri-infarct areas in Tg-Nox4, compared with littermate controls. In cultured brain pericytes, Nox4 was significantly upregulated by hypoxia and was promptly downregulated by reoxygenation. Phosphorylation of NFkB and production of matrix metalloproteinase 9 were significantly increased in both cultured pericytes overexpressing Nox4 and in periinfarct areas in Tg-Nox4. Collectively, Nox4 is upregulated in pericytes in peri-infarct areas after acute brain ischemia and may enhance blood-brain barrier breakdown through activation of NFkB and matrix metalloproteinase 9, thereby causing enlargement of infarct volume.

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Alterations in the time course of expression of the Nox family in the brain in a rat experimental cerebral ischemia and reperfusion model: effects of melatonin

Cited by 74 publications

References 35 publications

Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats

Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats

NADPH oxidase in brain injury and neurodegenerative disorders

Detrimental role of pericyte Nox4 in the acute phase of brain ischemia

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