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https://www.readbyqxmd.com/read/28442737/structural-and-biochemical-insights-of-cypa-and-aif-interaction
#1
Biancamaria Farina, Gianluigi Di Sorbo, Angela Chambery, Andrea Caporale, Guido Leoni, Rosita Russo, Fabiola Mascanzoni, Domenico Raimondo, Roberto Fattorusso, Menotti Ruvo, Nunzianna Doti
The Cyclophilin A (CypA)/Apoptosis Inducing Factor (AIF) complex is implicated in the DNA degradation in response to various cellular stress conditions, such as oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury. The pro-apoptotic form of AIF (AIF(Δ1-121)) mainly interacts with CypA through the amino acid region 370-394. The AIF(370-394) synthetic peptide inhibits complex formation in vitro by binding to CypA and exerts neuroprotection in a model of glutamate-mediated oxidative stress. Here, the binding site of AIF(Δ1-121) and AIF(370-394) on CypA has been mapped by NMR spectroscopy and biochemical studies, and a molecular model of the complex has been proposed...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423529/pif-promotes-brain-re-myelination-locally-while-regulating-systemic-inflammation-clinically-relevant-multiple-sclerosis-m-smegmatis-model
#2
Giuseppe Migliara, Martin Mueller, Alessia Piermattei, Chaya Brodie, Michael J Paidas, Eytan R Barnea, Francesco Ria
Neurologic disease diagnosis and treatment is challenging. Multiple Sclerosis (MS) is a demyelinating autoimmune disease with few clinical forms and uncertain etiology. Current studies suggest that it is likely caused by infection(s) triggering a systemic immune response resulting in antigen/non-antigen-related autoimmune response in central nervous system (CNS). New therapeutic approaches are needed. Secreted by viable embryos, PreImplantation Factor (PIF) possesses a local and systemic immunity regulatory role...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414037/spatio-temporal-regulation-of-connexin43-phosphorylation-and-gap-junction-dynamics
#3
REVIEW
Joell L Solan, Paul D Lampe
Gap junctions are specialized membrane domains containing tens to thousands of intercellular channels. These channels permit exchange of small molecules (<1000Da) including ions, amino acids, nucleotides, metabolites and secondary messengers (e.g., calcium, glucose, cAMP, cGMP, IP3) between cells. The common reductionist view of these structures is that they are composed entirely of integral membrane proteins encoded by the 21 member connexin human gene family. However, it is clear that the normal physiological function of this structure requires interaction and regulation by a variety of proteins, especially kinases...
April 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28400714/deletion-of-trpc6-attenuates-nmda-receptor-mediated-ca-2-entry-and-ca-2-induced-neurotoxicity-following-cerebral-ischemia-and-oxygen-glucose-deprivation
#4
Jin Chen, Zhaozhong Li, Jeffery T Hatcher, Qing-Hui Chen, Li Chen, Robert D Wurster, Sic L Chan, Zixi Cheng
Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na(+) and Ca(2+) and are widely expressed in the brain. In this study, the role of TRPC6 was investigated following ischemia/reperfusion (I/R) and oxygen-glucose deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT) mice cortical neurons following I/R and in primary neurons with OGD, and that deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD- /neurotoxin-induced neuronal death. Using live-cell imaging to examine intracellular Ca(2+) levels ([Ca(2+)] i ), we found that OGD induced a significant higher increase in glutamate-evoked Ca(2+) influx compared to untreated control and such an increase was reduced by TRPC6 deletion...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28397127/a-novel-strategy-to-enhance-angiogenesis-in-vivo-using-the-small-vegf-binding-peptide-pr1p
#5
Avner Adini, Irit Adini, Zai-Long Chi, Ratmir Derda, Amy E Birsner, Benjamin D Matthews, Robert J D'Amato
Therapeutic angiogenesis is an experimental frontier in vascular biology that seeks to deliver angiogenic growth factors to ischemic or injured tissues to promote targeted formation of new blood vessels as an alternative approach to surgical revascularization procedures. Vascular endothelial growth factor (VEGF) is a potent angiogenic signal protein that is locally upregulated at sites of tissue injury. However, therapies aimed at increasing VEGF levels experimentally by injecting VEGF gene or protein failed to improve outcomes in human trials in part due to its short half-life and systemic toxicity...
April 10, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28290048/carnosine-modulates-nitric-oxide-in-stimulated-murine-raw-264-7-macrophages
#6
Giuseppe Caruso, Claudia G Fresta, Francisco Martinez-Becerra, Lopalco Antonio, Ryan T Johnson, Richard P S de Campos, Joseph M Siegel, Manjula B Wijesinghe, Giuseppe Lazzarino, Susan M Lunte
Excess nitric oxide (NO) production occurs in several pathological states, including neurodegeneration, ischemia, and inflammation, and is generally accompanied by increased oxidative/nitrosative stress. Carnosine [β-alanine-histidine (β-Ala-His)] has been reported to decrease oxidative/nitrosative stress-associated cell damage by reducing the amount of NO produced. In this study, we evaluated the effect of carnosine on NO production by murine RAW 264.7 macrophages stimulated with lipopolysaccharides + interferon-γ...
March 13, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28272706/gc-ms-based-metabolomic-analysis-of-alleviated-renal-ischemia-reperfusion-injury-induced-by-remote-ischemic-preconditioning
#7
S Shen, J-F Wang, J-Q Wu, J-X Zhou, S-D Meng, J Ma, C -L Zhu, G-G Deng, D Liu
OBJECTIVE: Dysfunctional metabolisms have contributed towards ischemia-reperfusion (I/R) injury. However, the role of remote ischemic preconditioning (RIP) in I/R injury is not well known. The present study showed alleviated I/R injury in kidneys treated with RIP. MATERIALS AND METHODS: We utilized GC/MS-based metabolomics to characterize the variation of metabolomes. RESULTS: Metabolic category using differential metabolites showed the lower percentage of amino acids in I/R group in comparison to RIP+I/R group, confirming the importance of amino acid metabolism in RIP-treated rat kidney...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28250763/molecular-chaperones-and-hypoxic-ischemic-encephalopathy
#8
REVIEW
Cong Hua, Wei-Na Ju, Hang Jin, Xin Sun, Gang Zhao
Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28210876/effect-of-hyperhomocysteinemia-on-redox-balance-and-redox-defence-enzymes-in-ischemia-reperfusion-injury-and-or-after-ischemic-preconditioning-in-rats
#9
Martin Petráš, Anna Drgová, Mária Kovalská, Zuzana Tatarková, Barbara Tóthová, Oľga Križanová, Ján Lehotský
Increased level of homocysteine (hHcy) in plasma is an accompanying phenomenon of many diseases, including a brain stroke. This study determines whether hyperhomocysteinemia (which is a risk factor of brain ischemia) itself or in combination with ischemic preconditioning affects the ischemia-induced neurodegenerative changes, generation of reactive oxygen species (ROS), lipoperoxidation, protein oxidation, and activity of antioxidant enzymes in the rat brain cortex. The hHcy was induced by subcutaneous administration of homocysteine (0...
February 16, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28178567/defective-branched-chain-amino-acid-catabolism-disrupts-glucose-metabolism-and-sensitizes-the-heart-to-ischemia-reperfusion-injury
#10
Tao Li, Zhen Zhang, Stephen C Kolwicz, Lauren Abell, Nathan D Roe, Maengjo Kim, Bo Zhou, Yang Cao, Julia Ritterhoff, Haiwei Gu, Daniel Raftery, Haipeng Sun, Rong Tian
Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown. In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury. High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28164762/regulation-of-ion-channels-cellular-carriers-and-na-k-atpase-by-janus-kinase-3
#11
Mentor Sopjani, Shpëtim Thaçi, Berat Krasniqi, Miranda Selmonaj, Mark Rinnerthaler, Miribane Dërmaku-Sopjani
Janus kinase-3 (JAK3), a tyrosine kinase, is expressed in a variety of tissues, including the brain, and is involved in the signaling of cytokine receptors. JAK3 participates in numerous functions, among other the cell survival and proliferation, neuroprotection, apoptosis, as well as cellular response to hypoxia and ischemia-reperfusion. This kinase further contributes in the signaling of hematopoietic cell cytokine receptors, dendritic cells activation, maturation, and immune suppression as well as to cell volume regulation...
February 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28106291/ocular-effects-of-sulfur-mustard-and-therapeutic-approaches-a-review
#12
Yunes Panahi, Seyyed Mahdi Rajaee, Amirhossein Sahebkar
Sulfur mustard (SM) is a strong blistering, highly reactive, lipophilic chemical war agent that causes injury in different organs including the skin, eyes and respiratory tract. The Eyes are especially susceptible to the consequences of SM poisoning because of the aqueous and mucosal nature of conjunctiva and cornea. DNA alkylation and depletion of glutathione, are the most important mechanisms of SM action in the eye injuries. Acute clinical symptoms are including decrease in visual acuity, dryness, photophobia, blepharospasm, conjunctivitis and complaints of foreign body sensation and soreness that gradually progress to severe ocular pain...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27992175/label-free-electrochemical-biosensor-for-monitoring-of-chloride-ion-in-an-animal-model-of-alzhemier-s-disease
#13
Hui Dong, Limin Zhang, Wei Liu, Yang Tian
The potential damage of Alzheimer's disease (AD) in brain function has attracted extensive attention. As the most common anion, Cl(-) has been indicated to play significant roles in brain diseases, particularly in the pathological process of AD. In this work, a label-free selective and accurate electrochemical biosensor was first developed for real-time monitoring of Cl(-) levels in a mouse brain model of AD and rat brain upon global cerebral ischemia. Silver nanoparticles (AgNPs) were designed and synthesized as selective recognition element for Cl(-), while 5'-MB-GGCGCGATTTT-SH-3' (SH-DNA-MB, MB = methylene blue) was selected as an inner reference molecule for a built-in correction to avoid the effects from the complicated brain...
December 19, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27991798/comfortably-numb-and-back-plasma-metabolomics-reveals-biochemical-adaptations-in-the-hibernating-13-lined-ground-squirrel
#14
Angelo D'Alessandro, Travis Nemkov, Lori K Bogren, Sandra L Martin, Kirk C Hansen
Hibernation is an evolutionary adaptation that affords some mammals the ability to exploit the cold to achieve extreme metabolic depression (torpor) while avoiding ischemia/reperfusion or hemorrhagic shock injuries. Hibernators cycle periodically out of torpor, restoring high metabolic activity. If understood at the molecular level, the adaptations underlying torpor-arousal cycles may be leveraged for translational applications in critical fields such as intensive care medicine. Here, we monitored 266 metabolites to investigate the metabolic adaptations to hibernation in plasma from 13-lined ground squirrels (57 animals, 9 time points)...
December 29, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27974423/vegf165b-modulates-endothelial-vegfr1-stat3-signaling-pathway-and-angiogenesis-in-human-and-experimental-peripheral-arterial-disease
#15
Vijay Chaitanya Ganta, Min Choi, Anna Kutateladze, Brian H Annex
RATIONALE: Atherosclerotic-arterial occlusions decrease tissue perfusion causing ischemia to lower limbs in patients with peripheral arterial disease (PAD). Ischemia in muscle induces an angiogenic response, but the magnitude of this response is frequently inadequate to meet tissue perfusion requirements. Alternate splicing in the exon-8 of vascular endothelial growth factor (VEGF)-A results in production of proangiogenic VEGFxxxa isoforms (VEGF165a, 165 for the 165 amino acid product) and antiangiogenic VEGFxxxb (VEGF165b) isoforms...
January 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/27934126/selective-and-sensitive-monitoring-of-cerebral-antioxidants-based-on-the-dye-labeled-dna-polydopamine-conjugates
#16
Shishi Ma, Yan-Xia Qi, Xiao-Qin Jiang, Jie-Qiong Chen, Qiao-Yu Zhou, Guoyue Shi, Min Zhang
A simple and novel method for evaluating antioxidants in complex biological fluids has been developed based on the interaction of dye-labeled single-strand DNA (ssDNA) and polydopamine (PDA). Due to the interaction between ssDNA and PDA, the fluorescence of dye-labeled ssDNA (e.g., FITC-ssDNA, as donor) can be quenched by PDA (as acceptor) to the fluorescence "off" state through Förster resonance energy transfer (FRET). However, in the presence of various antioxidants, such as glutathione (GSH), ascorbic acid (AA), cysteine (Cys), and homocysteine (Hcys), the spontaneous oxidative polymerization reaction from DA to PDA would be blocked, resulting in the freedom of FITC-ssDNA and leading to the fluorescence "on" state...
December 6, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27884929/pro-nociceptive-migraine-mediator-cgrp-provides-neuroprotection-of-sensory-cortical-and-cerebellar-neurons-via-multi-kinase-signaling
#17
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
#18
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
#19
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...
December 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
#20
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...
February 2017: Biochimica et Biophysica Acta
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