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ischemia and amino acid

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
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
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
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...
2016: Journal of the American Heart Association
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
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
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
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
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
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
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
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
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
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
Savitree T Charununtakorn, Nattayaporn Apaijai, Sasiwan Kerdphoo, Krekwit Shinlapawittayatorn, Siriporn C Chattipakorn, Nipon Chattipakorn
AIM: Myocardial reperfusion via the re-canalization of occluded coronary arteries is gold standard for the treatment of acute myocardial infarction. However, reperfusion itself can cause myocardial damage due to increased reactive oxygen species (ROS) production, a process known as ischemia/reperfusion (I/R) injury. Cardiac mitochondria are the major organelle of ROS production in the heart. Cardiac mitochondrial dysfunction caused by an increased ROS production can increase cardiac arrhythmia incidence, myocardial infarct size and cardiac dysfunction...
July 19, 2016: Cardiovascular Therapeutics
Ming-Hua Li, Tian-Dong Leng, Xue-Chao Feng, Tao Yang, Roger P Simon, Zhi-Gang Xiong
An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis...
August 26, 2016: Journal of Biological Chemistry
Kaneto Tamura, Nobuhiko Hayashi, Joseph George, Nobuyuki Toshikuni, Tomiyasu Arisawa, Jun Hiratake, Mutsumi Tsuchishima, Mikihiro Tsutsumi
Ischemia-reperfusion (IR) injury is a major clinical problem and is associated with numerous adverse effects. GGsTop [2-amino-4{[3-(carboxymethyl)phenyl](methyl)phosphono}butanoic acid] is a highly specific and irreversible γ-glutamyl transpeptidase (γ-GT) inhibitor. We studied the protective effects of GGsTop on IR-induced hepatic injury in rats. Ischemia was induced by clamping the portal vein and hepatic artery of left lateral and median lobes of the liver. Before clamping, saline (IR group) or saline containing 1 mg/kg body wt of GGsTop (IR-GGsTop group) was injected into the liver through the inferior vena cava...
August 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Hongbin Fan, Xiaoquan Li, Wei Wang, Qingwei Lai, Xiaohong Tang, Dianshuai Gao, Xiaoxing Yin, Tiejun Xu
Neonatal hypoxia-ischemia brain damage is an important cause of death by affecting prognosis of neural diseases. It is difficult to find effective methods of prevention and treatment due to the complexity of its pathogenesis. N-methyl-D-aspartate (NMDA), as an excitotoxicity amino acids, has proven to play an important role in hypoxic-ischemic. However, the exact effects of the NMDA subunits, NR2A and NR2B, during hypoxic-ischemic have not been investigated in detail. Therefore, we sought to study whether the NMDA receptor antagonist could confer neuroprotective effects in a neonatal rat hypoxia-ischemia model...
November 2015: Cell Biochemistry and Biophysics
Hidemasa Katsumi, Makiya Nishikawa, Rikiya Hirosaki, Tatsuya Okuda, Shigeru Kawakami, Fumiyoshi Yamashita, Mitsuru Hashida, Toshiyasu Sakane, Akira Yamamoto
To inhibit hepatic ischemia/reperfusion injury, we developed polyethylene glycol (PEG) conjugated (PEGylated) cysteine-modified lysine dendrimers with multiple reduced thiols, which function as scavengers of reactive oxygen species (ROS). Second, third, and fourth generation (K2, K3, and K4) highly branched amino acid spherical lysine dendrimers were synthesized, and cysteine (C) was conjugated to the outer layer of these lysine dendrimers to obtain K2C, K3C, and K4C dendrimers. Subsequently, PEG was reacted with the C residues of the dendrimers to obtain PEGylated dendrimers with multiple reduced thiols (K2C-PEG, K3C-PEG, and K4C-PEG)...
August 1, 2016: Molecular Pharmaceutics
Xiao-xiao Li, Sheng-feng Lu, Bing-mei Zhu, Shu-ping Fu
Excitatory amino acids toxicity is an onset causation of cerebral ischemia injury cascade reaction, and eventually leading to brain cell necrosis and apoptosis. Acupuncture is reported to be effective for ischemic stroke in clinical practice and animal experiments, but its mechanism is still under exploring. In this paper the authors introduce the research status of antiexcitatory amino acids toxicity effect of acupuncture in ischemic stroke animals by summarizing its effects on subunits of ionotropic glutamate receptor (NMDA/AMPA) and metabotropic glutamate receptors (mGluRs), and on astrocyte activities...
April 2016: Zhen Ci Yan Jiu, Acupuncture Research
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