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https://www.readbyqxmd.com/read/27884929/pro-nociceptive-migraine-mediator-cgrp-provides-neuroprotection-of-sensory-cortical-and-cerebellar-neurons-via-multi-kinase-signaling
#1
Polina A Abushik, Geneviève Bart, Paula Korhonen, Hanna Leinonen, Raisa Giniatullina, Dmitry A Sibarov, Anna-Liisa Levonen, Tarja Malm, Sergei M Antonov, Rashid Giniatullin
BACKGROUND: Blocking the pro-nociceptive action of CGRP is one of the most promising approaches for migraine prophylaxis. The aim of this study was to explore a role for CGRP as a neuroprotective agent for central and peripheral neurons. METHODS: The viability of isolated rat trigeminal, cortical and cerebellar neurons was tested by fluorescence vital assay. Engagement of Nrf2 target genes was analyzed by qPCR. The neuroprotective efficacy of CGRP in vivo was tested in mice using a permanent cerebral ischemia model...
November 24, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27881952/tissue-type-plasminogen-activator-tpa-modulates-the-postsynaptic-response-of-cerebral-cortical-neurons-to-the-presynaptic-release-of-glutamate
#2
Valerie Jeanneret, Fang Wu, Paola Merino, Enrique Torre, Ariel Diaz, Lihong Cheng, Manuel Yepes
Tissue-type plasminogen activator (tPA) is a serine proteinase released by the presynaptic terminal of cerebral cortical neurons following membrane depolarization (Echeverry et al., 2010). Recent studies indicate that the release of tPA triggers the synaptic vesicle cycle and promotes the exocytosis (Wu et al., 2015) and endocytic retrieval (Yepes et al., 2016) of glutamate-containing synaptic vesicles. Here we used electron microscopy, proteomics, quantitative phosphoproteomics, biochemical analyses with extracts of the postsynaptic density (PSD), and an animal model of cerebral ischemia with mice overexpressing neuronal tPA to study whether the presynaptic release of tPA also has an effect on the postsynaptic terminal...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27832938/keto-acid-metabolites-of-branched-chain-amino-acids-inhibit-oxidative-stress-induced-necrosis-and-attenuate-myocardial-ischemia-reperfusion-injury
#3
Weibing Dong, Meiyi Zhou, Mei Dong, Bangfen Pan, Yunxia Liu, Jing Shao, Xiaoping Gu, Ying Huang, Guangping Li, Yibin Wang, Haipeng Sun
Branched chain α-keto acids (BCKAs) are endogenous metabolites of branched-chain amino acids (BCAAs). BCAA and BCKA are significantly elevated in pathologically stressed heart and contribute to chronic pathological remodeling and dysfunction. However, their direct impact on acute cardiac injury is unknown. Here, we demonstrated that elevated BCKAs significantly attenuated ischemia-reperfusion (I/R) injury and preserved post I/R function in isolated mouse hearts. BCKAs protected cardiomyocytes from oxidative stress-induced cell death in vitro...
November 8, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27816754/characterizing-the-mode-of-action-of-extracellular-connexin43-channel-blocking-mimetic-peptides-in-an-in-vitro-ischemia-injury-model
#4
Yeri Kim, Jarred M Griffin, Paul W R Harris, Sin Hang Crystal Chan, Louise F B Nicholson, Margaret A Brimble, Simon J O'Carroll, Colin R Green
BACKGROUND: Non-selective Connexin43 hemichannels contribute to secondary lesion spread. The hemichannel blocking peptidomimetic Peptide5, derived from the second extracellular loop of the human Connexin43 protein, prevents lesion spread and reduces vascular permeability in preclinical models of central nervous system injury. The molecular mode of action of Peptide5, however, was unknown and is described here. METHODS: Human cerebral microvascular endothelial cells and APRE-19 cells were used...
November 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27803669/the-role-of-hydrogen-sulfide-in-renal-system
#5
REVIEW
Xu Cao, Jin-Song Bian
Hydrogen sulfide has gained recognition as the third gaseous signaling molecule after nitric oxide and carbon monoxide. This review surveys the emerging role of H2S in mammalian renal system, with emphasis on both renal physiology and diseases. H2S is produced redundantly by four pathways in kidney, indicating the abundance of this gaseous molecule in the organ. In physiological conditions, H2S was found to regulate the excretory function of the kidney possibly by the inhibitory effect on sodium transporters on renal tubular cells...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27793236/isoflurane-provides-neuroprotection-in-neonatal-hypoxic-ischemic-brain-injury-by-suppressing-apoptosis
#6
De-An Zhao, Ling-Yun Bi, Qian Huang, Fang-Min Zhang, Zi-Ming Han
BACKGROUND AND OBJECTIVES: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism...
November 2016: Brazilian Journal of Anesthesiology
https://www.readbyqxmd.com/read/27768719/rlj-rgd3-a-novel-recombinant-toxin-protein-from-lampetra-japonica-protects-against-cerebral-reperfusion-injury-following-middle-cerebral-artery-occlusion-involving-the-integrin-pi3k-akt-pathway-in-rats
#7
Qian Lu, Jihong Wang, Junshu Jiang, Shengnan Wang, Qilan Jia, Yue Wang, Weiping Li, Qin Zhou, Li Lv, Qingwei Li
BACKGROUND: The RGD-toxin protein Lj-RGD3 is a naturally occurring 118 amino acid peptide that can be obtained from the salivary gland of the Lampetra japonica fish. This unique peptide contains 3 RGD (Arg-Gly-Asp) motifs in its primary structure. Lj-RGD3 is available in recombinant form (rLj-RGD3) and can be produced in large quantities using DNA recombination techniques. The pharmacology of the three RGD motif-containing peptides has not been studied. This study investigated the protective effects of rLj-RGD3, a novel polypeptide, against ischemia/reperfusion-induced damage to the brain caused by middle cerebral artery occlusion (MCAO) in a rat stroke model...
2016: PloS One
https://www.readbyqxmd.com/read/27768124/neovascularization-and-functional-recovery-after-intracerebral-hemorrhage-is-conditioned-by-the-tp53-arg72pro-single-nucleotide-polymorphism
#8
Cristina Rodríguez, Tomás Sobrino, Jesús Agulla, Verónica Bobo-Jiménez, María E Ramos-Araque, Juan J Duarte, José C Gómez-Sánchez, Juan P Bolaños, José Castillo, Ángeles Almeida
Intracerebral hemorrhage (ICH) is a devastating subtype of stroke that lacks effective therapy and reliable prognosis. Neovascularization following ICH is an essential compensatory response that mediates brain repair and modulates the clinical outcome of stroke patients. However, the mechanism that dictates this process is unknown. Bone marrow-derived endothelial progenitor cells (EPCs) promote endothelial repair and contribute to ischemia-induced neovascularization. The human Tp53 gene harbors a common single-nucleotide polymorphism (SNP) at codon 72, which yields an arginine-to-proline amino-acidic substitution (Arg72Pro) that modulates the apoptotic activity of the p53 protein...
October 21, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27666815/role-of-galectin-3-in-autoimmune-and-non-autoimmune-nephropathies
#9
Francesca Saccon, Mariele Gatto, Anna Ghirardello, Luca Iaccarino, Leonardo Punzi, Andrea Doria
Galectins are evolutionary conserved β-galactoside binding proteins with a carbohydrate-recognition domain (CRD) of approximately 130 amino acids. In mammals, 15 members of the galectin family have been identified and classified into three subtypes according to CRD organization: prototype, tandem repeat-type and chimera-type galectins. Galectin-3 (gal-3) is the only chimera type galectin in vertebrates containing one CRD linked to an unusual long N-terminal domain which displays non-lectin dependent activities...
September 23, 2016: Autoimmunity Reviews
https://www.readbyqxmd.com/read/27664804/metabolic-signature-of-remote-ischemic-preconditioning-involving-a-cocktail-of-amino-acids-and-biogenic-amines
#10
Juan Manuel Chao de la Barca, Oussama Bakhta, Hussein Kalakech, Gilles Simard, Sophie Tamareille, Véronique Catros, Jacques Callebert, Cédric Gadras, Lydie Tessier, Pascal Reynier, Fabrice Prunier, Delphine Mirebeau-Prunier
BACKGROUND: Remote ischemic preconditioning (RIPC) is an attractive therapeutic procedure for protecting the heart against ischemia/reperfusion injury. Despite evidence of humoral mediators transported through the circulation playing a critical role, their actual identities so far remain unknown. We sought to identify plasmatic RIPC-induced metabolites that may play a role. METHODS AND RESULTS: Rat plasma samples from RIPC and control groups were analyzed using a targeted metabolomic approach aimed at measuring 188 metabolites...
September 24, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27651151/long-noncoding-rna-meg3-activation-of-p53-mediates-ischemic-neuronal-death-in-stroke
#11
Honglin Yan, Jingping Yuan, Likun Gao, Jie Rao, Jichang Hu
Maternally expressed gene 3 (MEG3) is suggested to function as a long non-coding RNA (lncRNA) and to play roles in various human cancers. However, the functional properties of MEG3 in ischemic stroke remain unknown. Here, we report that expression of MEG3 is upregulated following ischemia in adult mice. Moreover, cerebral ischemia recruits p53 into the MEG3 complex in ischemic tissues. MEG3 directly binds with the p53 DNA binding domain (DBD) consisting of amino acids 271-282 (p53-DBD(271)(-)(282)), which stimulates p53-mediated transactivation and mediates ischemic neuronal death...
September 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27637994/-isoflurane-provides-neuroprotection-in-neonatal-hypoxic-ischemic-brain-injury-by-suppressing-apoptosis
#12
De-An Zhao, Ling-Yun Bi, Qian Huang, Fang-Min Zhang, Zi-Ming Han
BACKGROUND AND OBJECTIVES: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism...
September 13, 2016: Revista Brasileira de Anestesiologia
https://www.readbyqxmd.com/read/27586187/formulation-of-hydrophobic-therapeutics-with-self-assembling-peptide-and-amino-acid-a-new-platform-for-intravenous-drug-delivery
#13
Shaun Pacheco, Takashi Kanou, Shan-Yu Fung, Kenny Chen, Daiyoon Lee, Xiaohui Bai, Shaf Keshavjee, Mingyao Liu
Clinical application of hydrophobic therapeutics is restricted by lack of an efficient vehicle which permits their solubility in aqueous environments. We have previously developed a novel formulation strategy to deliver a hydrophobic Src inhibitor, PP2, involving combinations of one self-assembling peptide (SAP) and one of 4 selected amino acids (AAs). The present study aims to develop a generalized drug delivery platform for intravenous application of hydrophobic drugs by combining self-assembling peptide, amino acid and low concentration of co-solvent...
October 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27555478/activation-of-the-na-h-exchanger-in-isolated-cardiomyocytes-through-%C3%AE-raf-dependent-pathways-role-of-thr-653-of-the-cytosolic-tail
#14
Xiuju Li, Aruna Augustine, Difei Sun, Liang Li, Larry Fliegel
The mammalian Na(+)/H(+) exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that is a key regulator of intracellular pH in isolated cardiomyocytes.A 500 amino acid membrane domain removes protons and is regulated by a 315 amino acid cytosolic domain.In the myocardium, aberrant regulation of NHE1 contributes to ischemia reperfusion damage and to heart hypertrophy.We examined mechanisms of regulation of NHE1 in the myocardium by endothelin and β-Raf.Endothelin stimulated NHE1 activity and activated Erk-dependent pathways...
August 20, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27516569/biochemistry-and-therapeutic-potential-of-hydrogen-sulfide-reality-or-fantasy
#15
Paulina Brodek, Beata Olas
Hydrogen sulfide (H2S) is a signaling gasotransmitter, involved in different physiological and pathological processes. H2S regulates apoptosis, the cell cycle and oxidative stress. H2S exerts powerful effects on smooth muscle cells, endothelial cells, inflammatory cells, endoplasmic reticulum, mitochondria and nuclear transcription factors. H2S is known to be produced from L-cysteine, D-cysteine and L-homocysteine in the body. Four enzymes - cystathionine-b synthase (CBS), mercaptopyruvate sulfurtransferase (3-MST), cystathionine-γ lyase (CSE) and cysteine aminotransferase (CAT) - are involved in H2S synthesis...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/27515399/a-novel-in-vitro-cypd-mediated-p53-aggregation-assay-suggests-a-model-for-mitochondrial-permeability-transition-by-chaperone-systems
#16
Ivan Lebedev, Alice Nemajerova, Zachariah H Foda, Maja Kornaj, Michael Tong, Ute M Moll, Markus A Seeliger
Tissue necrosis as a consequence of ischemia-reperfusion injury and oxidative damage is a leading cause of permanent disability and death worldwide. The complete mechanism by which cells undergo necrosis upon oxidative stress is not understood. In response to an oxidative insult, wild-type p53 has been implicated as a central regulatory component of the mitochondrial permeability transition (mPT), triggering necrosis. This process is associated with cellular stabilization and translocation of p53 into the mitochondrial matrix...
October 9, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27505423/intestinal-microbial-metabolites-are-linked-to-severity-of-myocardial-infarction-in-rats
#17
Vy Lam, Jidong Su, Anna Hsu, Garrett J Gross, Nita H Salzman, John E Baker
Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days with the non-absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin was analyzed using mass spectrometry-based metabolite profiling platforms. Antibiotic-induced changes in the abundance of individual groups of intestinal microbiota dramatically altered the host's metabolism...
2016: PloS One
https://www.readbyqxmd.com/read/27478806/the-relation-between-gaba-and-l-arginine-levels-with-some-stroke-risk-factors-in-acute-ischemic-stroke-patients
#18
Mohsen Hosinian, Durdi Qujeq, Alijan Ahmadi Ahangar
Changes in extra and intracellular neurotransmitter amino acids concentration in the early stage of acute cerebral ischemia have been reported. In this the study, serum level of gamma aminobutyric acid (GABA) and L-Arginine in acute ischemic stroke patients was assessed. 60 patients with acute ischemic stroke and sixthy healthy volunteers as a control group were assessed. Serum GABA was measured with modified enzymatic method and serum L- Arginine was measured by modified Sakaguchi method. Serum GABA level in stroke cases was lower than that of the control group...
2016: International Journal of Molecular and Cellular Medicine
https://www.readbyqxmd.com/read/27468268/blood-biomarkers-for-evaluation-of-perinatal-encephalopathy
#19
REVIEW
Ernest M Graham, Irina Burd, Allen D Everett, Frances J Northington
Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27455572/-peculiarities-of-the-cerebrovascular-effects-of-glutamic-acid
#20
T S Gan'shina, E V Kurza, I N Kurdyumov, D V Maslennikov, R S Mirzoyan
Experiments on nonlinear rats subjected to global transient cerebral ischemia revealed the ability of glutamic acid to improve cerebral circulation. Consequently, the excitatory amino acid can produce adverse (neurotoxic) and positive (anti-ischemic) effects in cerebral ischemia. The cerebrovascular effect of glutamic acid in cerebral ischemia is attenuated on the background action of the MNDA receptor blocker MK-801 (0.5 mg/kg intravenously) and eliminated by bicuculline. When glutamic acid is combined with the non-competitive MNDA receptor antagonist MK-801, neither one nor another drug shows its vasodilator effect...
2016: Eksperimental'naia i Klinicheskaia Farmakologiia
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