Plasminogen and its fragments in rat brain: a plausible role for astrocytes in angiostatin generation

Tykhomyrov, А. A.; Nedzvetsky, V. S.; Ağca, Can Ali; Korsa, V. V.; Grinenko, T. V.

doi:10.15407/ubj89.02.043

Cited by 4 publications

(2 citation statements)

References 37 publications

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“…To our knowledge, no studies on the function of angiostatin in acute ischemic stroke have been performed. However, we have recently discovered angiostatin isoforms in brain tissue of rats and have found that astrocytes are able to constistently produce angiostatins [50]. Our present investigation reveals that citicoline treatment of patients with acute ischemic stroke decreased anti-angiogenic signalling, specifically implicating angiostatin.…”

Section: Dynamics Of Clinical and Laboratory Parameters In Patients Wsupporting

confidence: 49%

Citicoline affects serum angiostatin and neurospecific protein levels in patients with atrial fibrillation and ischemic stroke

Tykhomyrov¹,

Kushnir²,

Nedzvetsky³

et al. 2019

Ukr.Biochem.J.

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Ischemic stroke is considered as one of the most frequent and severe complications of atrial fibrillation. The present study was undertaken to examine whether post-insult treatment with cytidine diphosphate-choline (CDP-choline, or citicoline) affects serum levels of the angiogenesis inhibitor angiostatin and neurospecific proteins as markers of brain damage in patients with cerebral ischemia associated with atrial fibrillation. Thirty-three patients with a diagnosis of acute ischemic stroke received citicoline sodium by intravenous infusions (1,000 mg daily for 14 days) in addition to the standard treatment (basic group). Twentyfive patients with the same pathologies, who received only standard therapy, were enrolled in the study as a control group. Serum content of angiostatin and neurospecific proteins, namely neurofilament heavy subunit (NF-H) and glial fibrillary acidic protein (GFAP), was measured by immunoblotting at the basal level and after the treatment. Citicoline treatment caused significant decreases in serum levels of angiostatin (by 40% vs. basal level, P < 0.05), GFAP (by 61%, P < 0.01), and the NF-H subunit (by 19%, P < 0.05) and had no effect on the serum albumin content. In contrast, there were no statistically significant differences between baseline levels of the studied protein markers and their content after the treatment period in the control group. These findings indicate for the first time that CDP-choline protects both astrocytes and neurons and improves angiogenic capacity through down-regulation of angiostatin in post-ischemic patients with atrial fibrillation after acute ischemic stroke. Further studies are needed to test associations between serum levels of these biomarkers, clinical outcomes, and treatment efficacy of stroke. K e y w o r d s: atrial fibrillation, ischemic stroke, citicoline, angiostatin, neurofilaments (NFs), glial fibrillary acidic protein (GFAP).I schemic stroke is a complex multifactorial and polygenic disease. It is generally accepted that one of the major risk factors for ischemic stroke is atrial fibrillation [1]. Past studies indicate that fibrillation of the atrium produces stasis of blood, which causes thrombus formation and embolism in the brain [2,3]. More recent investigations suggest that the pathogenesis of stroke in atrial fibrillation is more complicated and involves other factors in addition to the dysrhythmia [4,5]. It is well acknowled ged that atrial fibrillation is the most prevalent car-diac arrhythmia, affecting approximately 12% of the population worldwide. Being an independent risk factor for stroke, atrial fibrillation is associated with high mortality, morbidity, and socioeconomic burden [6]. Therefore, stroke prevention with appropriate prophylaxis remains central to management of both atrial fibrillation and its neurological complications. However, the search for effective neuroprotectors remains frustrating, and the current therapeutic protocols remain suboptimal. Ideally, sufficient protection must be provided to the ischemic brain a...

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Section: Dynamics Of Clinical and Laboratory Parameters In Patients Wsupporting

confidence: 49%

Citicoline affects serum angiostatin and neurospecific protein levels in patients with atrial fibrillation and ischemic stroke

Tykhomyrov¹,

Kushnir²,

Nedzvetsky³

et al. 2019

Ukr.Biochem.J.

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“…The initiation of programmed cell death is determined by evaluating the expression of proapoptotic proteins of the caspase family, Bcl family, and the relative content of cytochrome C in the cytosol compared to its mitochondrial pool (Tomiyama et al, 2010;Jemmerson et al, 2005). Given that glial cells provide all the needs of neurons to perform CNS functions, cultures of glial cells are considered adequate models for evaluating the neurotoxic effects of modern pollutants (Hoffman & Kalinich 2020;Tykhomyrov et al, 2017). Thus, the determination of apoptosis induction in an in vitro model of glial cells should reflect molecular and cellular damage that may be the cause of the neurotoxicity of pyrethroids.…”

Section: Introductionmentioning

confidence: 99%

Cypermethrin induces neurotoxicity via inhibition of glial cell viability and apoptosis initiation

Sukharenko,

Gasso

2022

TAVM

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The progress in agricultural productivity is accompanied by the increase in the global application of pesticides. Moreover, the number of different pesticides used is growing permanently all over the world. Several types of pesticides are effective tools to suppress the propagation of insects, bacteria, and fungi. However, they could correlate with toxicity for other non-targeted organisms including mammalian and humans. Neurotoxicity is considered to be the most detrimental effect of pesticides given the ecotoxicology studies of the environmental pollution consequences for the last decades. Exposure to neurotoxic pesticides can induce multiple harmful disturbances in the deregulation of vital molecular pathways, cellular response, and programmed cell death initiation as well as lead to a decline in the functioning of the central neural system (CNS). All of them are potent in inhibiting the adaptation mechanisms and viability of vertebrate populations. The pyrethroids are the most total used group of pesticides. This study of the neurotoxic effects of pyrethroids aimed to contribute to assessing the risk rate in the application of compromised chemicals in agriculture production. Glial cells are the prevailing population in the CNS. Measurement of the cytotoxic effect of pollutants can be assessed by their neurotoxicity in glial cell culture. In the present study, we detected glioma U251 cells' viability, oxidative stress indices, and a mitochondria-associated marker of apoptosis to evaluate the molecular mechanism of cypermethrin neurotoxicity. Obtained results have shown that 2 and 5 μg/ml doses of cypermethrin inhibited glioma U251 cell viability (p<0.05) and increased an oxidative stress level. Contrary, the dose of cypermethrin 1 μg/ml did not induce statistically significant both cell viability and oxidative stress. However, 2 and 5 μg/ml doses of cypermethrin exposure induced cytochrome C release to cytosol in a dose-dependent manner that is a marker of apoptosis initiation. Thus, the neurotoxic effect of pyrethroids can be mediated by the mitochondrial-dependent apoptotic pathway activation via cytochrome C release.

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Effects of a Propolis Extract on the Viability of and Levels of Cytoskeletal and Regulatory Proteins in Rat Brain Astrocytes: an In Vitro Study

et al. 2017

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Plasminogen and its fragments in rat brain: a plausible role for astrocytes in angiostatin generation

Abstract: The purpose of the present study was to examine the plasminogen localization and to detect levels of its fragments (angiostatins)

Cited by 4 publications

References 37 publications

Citicoline affects serum angiostatin and neurospecific protein levels in patients with atrial fibrillation and ischemic stroke

Citicoline affects serum angiostatin and neurospecific protein levels in patients with atrial fibrillation and ischemic stroke

Cypermethrin induces neurotoxicity via inhibition of glial cell viability and apoptosis initiation

Effects of a Propolis Extract on the Viability of and Levels of Cytoskeletal and Regulatory Proteins in Rat Brain Astrocytes: an In Vitro Study

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