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https://www.readbyqxmd.com/read/28634116/succinate-induced-neuronal-mitochondrial-fission-and-hexokinase-ii-malfunction-in-ischemic-stroke-therapeutical-effects-of-kaempferol
#1
Bin Wu, Hong Luo, Xu Zhou, Cai-Yi Cheng, Lin Lin, Bao-Lin Liu, Kang Liu, Ping Li, Hua Yang
Mitochondrial dysfunction is known as one of causative factors in ischemic stroke, leading to neuronal cell death. The present work was undertaken to investigate whether succinate induces neuron apoptosis by regulating mitochondrial morphology and function. In neurons, oxygen-glucose deprivation induced succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation, leading to mitochondrial fission. Kaempferol inhibited mitochondrial fission and maintained mitochondrial HK-II through activation of Akt, and thereby protected neurons from succinate-mediated ischemi injury...
June 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28634073/long-noncoding-rna-meg3-mediated-angiogenesis-after-cerebral-infarction-through-regulating-p53-nox4-axis
#2
Renya Zhan, Kangli Xu, Jianwei Pan, Qingsheng Xu, Shengjie Xu, Jian Shen
OBJECTIVE: This study aimed to explore the mechanism of lncRNA MEG3 on angiogenesis after cerebral infarction (CI). METHODS: The rat brain microvascular endothelial cells (RBMVECs) isolated from rat was used to establish CI model, which were treated with oxygen-glucose deprivation/reoxygenation (OGD/R). The genes mRNA and protein expression levels in RBMVECs were determined by the quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28630232/long-noncoding-rna-h19-promotes-neuroinflammation-in-ischemic-stroke-by-driving-histone-deacetylase-1-dependent-m1-microglial-polarization
#3
Jue Wang, Haiping Zhao, Zhibin Fan, Guangwen Li, Qingfeng Ma, Zhen Tao, Rongliang Wang, Juan Feng, Yumin Luo
BACKGROUND AND PURPOSE: Long noncoding RNA H19 is repressed after birth, but can be induced by hypoxia. We aim to investigate the impact on and underlying mechanism of H19 induction after ischemic stroke. METHODS: Circulating H19 levels in stroke patients and mice subjected to middle cerebral artery occlusion were assessed using real-time polymerase chain reaction. H19 siRNA and histone deacetylase 1 (HDAC1) plasmid were used to knock down H19 and overexpress HDAC1, respectively...
June 19, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28628081/o-glcnacylation-of-fumarase-maintains-tumour-growth-under-glucose-deficiency
#4
Ting Wang, Qiujing Yu, Jingjie Li, Bin Hu, Qin Zhao, Chunmin Ma, Wenhua Huang, Lingang Zhuo, Houqin Fang, Lujian Liao, Y Eugene Chin, Yuhui Jiang
Chromatin-associated fumarase (FH) affects histone methylation via its metabolic activity. However, whether this effect is involved in gene transcription remains to be clarified. In this study, we show that under glucose deprivation conditions, AMPK phosphorylates FH at Ser75, which in turn forms a complex with ATF2 and participates in promoter activation. FH-catalysed fumarate in promoter regions inhibits KDM2A demethylase activity, and thus maintains the H3K36me2 profile and facilitates gene expression for cell growth arrest...
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28627974/microrna-132-protects-hippocampal-neurons-against-oxygen-glucose-deprivation-induced-apoptosis
#5
Zu-Zhen Sun, Zhan-Yun Lv, Wen-Jing Tian, Yan Yang
Hypoxic-ischemic brain injury (HIBI) results in death or long-term neurologic impairment in both adults and children. In this study, we investigated the effects of microRNA-132 (miR-132) dysregulation on oxygen-glucose deprivation (OGD)-induced apoptosis in fetal rat hippocampal neurons, in order to reveal the therapeutic potential of miR-132 on HIBI. MiR-132 dysregulation was induced prior to OGD exposure by transfection of primary fetal rat hippocampal neurons with miR-132 mimic or miR-132 inhibitor. The effects of miR-132 overexpression and suppression on OGD-stimulated hippocampal neurons were evaluated by detection of cell viability, apoptotic cells rate, and the expression of apoptosis-related proteins...
June 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28627637/lentiviral-vector-mediated-co-overexpression-of-vegf-and-bcl-2-improves-mesenchymal-stem-cell-survival-and-enhances-paracrine-effects-in%C3%A2-vitro
#6
Xiaobin Ni, Caiwen Ou, Jingbin Guo, Bei Liu, Jianwu Zhang, Zhiye Wu, Hekai Li, Minsheng Chen
Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for ischemic heart disease; however, the low survival rate of transplanted cells limits their therapeutic efficacy. The aim of this study was to investigate whether the dual genetic modification of vascular endothelial growth factor (VEGF) and B‑cell lymphoma‑2 (Bcl‑2) confers a higher expression level of the target genes, better survival and a stronger paracrine effect in MSCs in an adverse environment than the modification of the individual genes...
June 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28624878/a-combination-of-three-repurposed-drugs-administered-at-reperfusion-as-a-promising-therapy-for-postischemic-brain-injury
#7
I-Chen Yu, Ping-Chang Kuo, Jui-Hung Yen, Hallel C Paraiso, Eric T Curfman, Benecia C Hong-Goka, Robert D Sweazey, Fen-Lei Chang
Cerebral ischemia leads to multifaceted injury to the brain. A polytherapeutic drug that can be administered immediately after reperfusion may increase protection to the brain by simultaneously targeting multiple deleterious cascades. This study evaluated efficacy of the combination of three clinically approved drugs: lamotrigine, minocycline, and lovastatin, using two mouse models: global and focal cerebral ischemia induced by transient occlusion of the common carotid arteries or the middle cerebral artery, respectively...
June 17, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28624412/mild-hypothermia-protects-hippocampal-neurons-against-oxygen-glucose-deprivation-reperfusion-induced-injury-by-improving-lysosomal-function-and-autophagic-flux
#8
Tianen Zhou, Lian Liang, Yanran Liang, Tao Yu, Chaotao Zeng, Longyuan Jiang
Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion(OGD/R)-induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered...
June 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28623280/ev-3-an-endogenous-human-erythropoietin-isoform-with-distinct-functional-relevance
#9
Christel Bonnas, Liane Wüstefeld, Daniela Winkler, Romy Kronstein-Wiedemann, Ekrem Dere, Katja Specht, Melanie Boxberg, Torsten Tonn, Hannelore Ehrenreich, Herbert Stadler, Inge Sillaber
Generation of multiple mRNAs by alternative splicing is well known in the group of cytokines and has recently been reported for the human erythropoietin (EPO) gene. Here, we focus on the alternatively spliced EPO transcript characterized by deletion of exon 3 (hEPOΔ3). We show co-regulation of EPO and hEPOΔ3 in human diseased tissue. The expression of hEPOΔ3 in various human samples was low under normal conditions, and distinctly increased in pathological states. Concomitant up-regulation of hEPOΔ3 and EPO in response to hypoxic conditions was also observed in HepG2 cell cultures...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621566/glutamate-dehydrogenase-is-essential-to-sustain-neuronal-oxidative-energy-metabolism-during-stimulation
#10
Michaela C Hohnholt, Vibe H Andersen, Jens V Andersen, Sofie K Christensen, Melis Karaca, Pierre Maechler, Helle S Waagepetersen
The enzyme glutamate dehydrogenase (GDH; Glud1) catalyzes the (reversible) oxidative deamination of glutamate to α-ketoglutarate accompanied by a reduction of NAD(+) to NADH. GDH connects amino acid, carbohydrate, neurotransmitter and oxidative energy metabolism. Glutamine is a neurotransmitter precursor used by neurons to sustain the pool of glutamate, but glutamine is also vividly oxidized for support of energy metabolism. This study investigates the role of GDH in neuronal metabolism by employing the Cns- Glud1(-/-) mouse, lacking GDH in the brain (GDH KO) and metabolic mapping using (13)C-labelled glutamine and glucose...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28619994/simultaneous-stimulation-of-glycolysis-and-gluconeogenesis-by-feeding-in-the-anterior-intestine-of-the-omnivorous-gift-tilapia-oreochromis-niloticus
#11
Yong-Jun Chen, Ti-Yin Zhang, Hai-Yan Chen, Shi-Mei Lin, Li Luo, De-Shou Wang
The present study was performed to investigate the roles of anterior intestine in the postprandial glucose homeostasis of the omnivorous Genetically Improved Farmed Tilapia (GIFT). Sub-adult fish (about 173 g) were sampled at 0, 1, 3, 8 and 24 h post feeding (HPF) after 36 h of food deprivation, and the time course of changes in intestinal glucose transport, glycolysis, glycogenesis and gluconeogenesis at the transcription and enzyme activity level, as well as plasma glucose contents, were analyzed. Compared with 0 HPF (fasting for 36 h), the mRNA levels of both ATP-dependent sodium/glucose cotransporter 1 and facilitated glucose transporter 2 increased during 1-3 HPF, decreased at 8 HPF and then leveled off...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28616574/therapeutic-arginine-starvation-in-ass1-deficient-cancers-inhibits-the-warburg-effect
#12
Jeff C Kremer, Brian A Van Tine
Argininosuccinate Synthetase 1 deficiency induces dependence on extracellular arginine for continued cellular growth and survival. Arginine starvation inhibits the Warburg effect and diverts glucose into serine biosynthesis, while simultaneously increasing glutamine metabolism via the tricarboxylic acid cycle. Simultaneous arginine deprivation and inhibition of the subsequent metabolic adaptations induce synthetic lethality.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28615161/high-glucose-increases-action-potential-firing-of-catecholamine-neurons-in-the-nucleus-of-the-solitary-tract-by-increasing-spontaneous-glutamate-inputs
#13
Brandon L Roberts, Mingyan Zhu, Huan Zhao, Crystal Dillon, Suzanne M Appleyard
Glucose is a crucial substrate essential for cell survival and function. Changes in glucose levels impact neuronal activity and glucose deprivation increases feeding. Several brain regions have been shown to respond to glucoprivation, including the nucleus of the solitary tract (NTS) in the brainstem. The NTS is the primary site in the brain that receives visceral afferent information from the gastrointestinal tract. The catecholaminergic (CA) subpopulation within the NTS modulates many homeostatic functions including cardiovascular reflexes, respiration, food intake, arousal and stress...
June 14, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28611773/fatty-acid-oxidation-compensates-for-lipopolysaccharide-induced-warburg-effect-in-glucose-deprived-monocytes
#14
Nora Raulien, Kathleen Friedrich, Sarah Strobel, Stefan Rubner, Sven Baumann, Martin von Bergen, Antje Körner, Martin Krueger, Manuela Rossol, Ulf Wagner
Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS) induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611253/n6-methyladenosine-is-required-for-the-hypoxic-stabilization-of-specific-mrnas
#15
Nate J Fry, Brittany A Law, Olga R Ilkayeva, Christopher L Holley, Kyle D Mansfield
Post-transcriptional regulation of mRNA during oxygen deprivation, or hypoxia, can affect the survivability of cells. Hypoxia has been shown to increase stability of a subset of ischemia-related mRNAs, including VEGF. RNA binding proteins and miRNAs have been identified as important for post-transcriptional regulation of individual mRNAs, but corresponding mechanisms that regulate global stability are not well understood. Recently, mRNA modification by N6-methyladenosine (m6A) has been shown to be involved in post-transcriptional regulation processes including mRNA stability and promotion of translation, but the role of m6A in the hypoxia response is unknown...
June 13, 2017: RNA
https://www.readbyqxmd.com/read/28610437/a-new-ferulic-acid-ester-from-rhodiola-wallichiana-var-cholaensis-crassulaceae
#16
Yaling Song, Jianming Zhou, Xuejing Wang, Xue Xie, Yiwu Zhao, Fuyong Ni, Wenzhe Huang, Zhenzhong Wang, Wei Xiao
A new ferulic acid ester, 6-feruloyloxyhexanoic acid (1), was isolated along with 10 known ones (2-11), from the concentrated water extract of Rhodiola wallichiana var. cholaensis. Their chemical structures were elucidated on the basis of extensive spectroscopic methods including Two-dimensional nuclear magnetic resonance (2D NMR) experiments. Compound 3 was isolated from this plant for the first time. The protective effects against H2O2-induced myocardial cell injury in cultured H9c2 cells were also evaluated...
June 14, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28603485/multifaceted-mechanisms-of-wy-14643-to-stabilize-the-blood-brain-barrier-in-a-model-of-traumatic-brain-injury
#17
Winfried Neuhaus, Tobias Krämer, Anja Neuhoff, Christina Gölz, Serge C Thal, Carola Y Förster
The blood-brain barrier (BBB) is damaged during ischemic insults such as traumatic brain injury or stroke. This contributes to vasogenic edema formation and deteriorate disease outcomes. Enormous efforts are pursued to understand underlying mechanisms of ischemic insults and develop novel therapeutic strategies. In the present study the effects of PPARα agonist WY-14643 were investigated to prevent BBB breakdown and reduce edema formation. WY-14643 inhibited barrier damage in a mouse BBB in vitro model of traumatic brain injury based on oxygen/glucose deprivation in a concentration dependent manner...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28602833/a-novel-il-1ra-pep-fusion-protein-with-enhanced-brain-penetration-ameliorates-cerebral-ischemia-reperfusion-injury-by-inhibition-of-oxidative-stress-and-neuroinflammation
#18
Dong-Dong Zhang, Min-Ji Zou, Ya-Tao Zhang, Wen-Liang Fu, Tao Xu, Jia-Xi Wang, Wen-Rong Xia, Zhi-Guang Huang, Xiang-Dong Gan, Xiao-Ming Zhu, Dong-Gang Xu
Neuroinflammation and oxidative stress are involved in cerebral ischemia-reperfusion, in which Interleukin 1 (IL-1), as an effective intervention target, is implicated. Interleukin-1 receptor antagonist (IL-1RA) is the natural inhibitor of IL-1, but blood-brain barrier (BBB) limits the brain penetration of intravenously administered IL-1RA, thereby restricting its therapeutic effect against neuroinflammation. In this study, we evaluated the potential effects of anti-inflammation and anti-oxidative stress of a novel protein IL-1RA-PEP, which fused IL-1RA with a cell penetrating peptide (CPP)...
June 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28598075/-the-protective-effect-of-tanshinone-iia-on-oxygen-glucose-deprivation-and-reperfusion-injury-of-microgliathrough-the-nlrp3-inflammatory-signaling-pathway
#19
Lin Cai, Xiao-Bo Yi, Li-Bang Yuan, Gu Gong
OBJECTIVES: To investigate the protective effect of Tanshinone IIA (TSA) on oxygen-glucose deprivation and reperfusion (OGD/R) injury of BV-2 cell and its NLRP3 inflammatory signaling pathway. METHODS: The highest expression level of NLPR3 in BV-2 cells was detected by Western blot after oxygen-glucose deprivation (OGD) for 3 h and reperfusion for different time, to determine the most suitable reperfusion time. Cell viability of TSA (0-2.5 ug/mL) treatment was detected by CCK8 assay to determine the maximum effect concentration of TSA...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28596571/the-role-of-trpc6-in-the-neuroprotection-of-calycosin-against-cerebral-ischemic-injury
#20
Chao Guo, Yongyuan Ma, Shanbo Ma, Fei Mu, Jiao Deng, Jialin Duan, Lize Xiong, Ying Yin, Yanhua Wang, Miaomaio Xi, Aidong Wen
Our previous studies have provided evidences that calycosin can protect the brain from ischemia/reperfusion injury, but its mechanisms is not fully understand. Transient receptor potential canonical 6 (TRPC6) has a critical role in promoting neuronal survival against cerebral ischemic injury. The aim of the present study is to test whether calycosin protects against cerebral ischemic injury through TRPC6-CREB pathway. In vivo, rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h and then treated with different doses of calycosin at the onset of reperfusion...
June 8, 2017: Scientific Reports
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