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https://www.readbyqxmd.com/read/27918235/comprehensive-mapping-of-5-hydroxymethylcytosine-epigenetic-dynamics-in-axon-regeneration
#1
Yong-Hwee Eddie Loh, Andrew Koemeter-Cox, Mattéa Finelli, Li Shen, Roland H Friedel, Hongyan Zou
In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5 hmC). We generated genome-wide 5 hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5 hmC changes that are associated with distinct signaling pathways...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27916987/weight-loss-induced-cellular-stress-in-subcutaneous-adipose-tissue-and-the-risk-for-weight-regain-in-overweight-and-obese-adults
#2
N J T Roumans, R G Vink, F G Bouwman, P Fazelzadeh, M A van Baak, E C M Mariman
BACKGROUND/OBJECTIVE: Weight loss is often followed by weight regain after the dietary intervention (DI). Cellular stress is increased in adipose tissue of obese individuals. However, the relation between cellular stress and weight regain is unclear. Previously, we observed increased adipose tissue cellular stress of participants regaining weight compared to participants maintaining weight loss. In the current study, we further investigated the relation between weight regain and changes in the expression of stress-related genes and stress protein levels to determine possible predictors of weight regain...
December 5, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27909249/mortalin-mediated-and-erk-controlled-targeting-of-hif-1%C3%AE-to-mitochondria-confers-resistance-to-apoptosis-under-hypoxia
#3
Ilias Mylonis, Maria Kourti, Martina Samiotaki, George Panayotou, George Simos
Hypoxia inducible factor-1 (HIF-1) is the main transcriptional activator of the cellular response to hypoxia and an important target of anticancer therapy. Phosphorylation by ERK stimulates the transcriptional activity of HIF-1α by inhibiting its CRM1-dependent nuclear export. Here, we demonstrate that phosphorylation by ERK also regulates the association of HIF-1α with a novel interaction partner identified as mortalin (GRP75) which mediates non-genomic involvement of HIF-1α in apoptosis. Mortalin binds specifically to HIF-1α lacking modification by ERK and their complex is localized outside the nucleus...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27903434/hypoxia-and-hif-1-activation-in-bacterial-infections
#4
Gayatri Devraj, Christiane Beerlage, Bernhard Brüne, Volkhard A J Kempf
For most of the living being, oxygen is one of the essential elements required to sustain life. Deprivation of oxygen causes tissue hypoxia and this affects host cell and organ functions severely. Tissue hypoxia is a prominent microenvironmental condition occurring in infections and there is a body of evidence that hypoxia and inflammation are interconnected with each other. The primary key factor mediating the mammalian hypoxic response is hypoxia inducible factor (HIF)-1, which regulates oxygen homeostasis on cellular, tissue and organism levels...
November 27, 2016: Microbes and Infection
https://www.readbyqxmd.com/read/27902314/newcastle-disease-virus-degrades-hif-1%C3%AE-through-proteasomal-pathways-independent-of-vhl-and-p53
#5
Noraini Abd-Aziz, Eric Stanbridge, Norazizah Shafee
Newcastle disease virus (NDV) is a candidate agent for oncolytic virotherapy. Despite its potential, the exact mechanism of its oncolysis is still not known. Recently, we reported that NDV exhibited an increased oncolytic activity in hypoxic cancer cells. These types of cells negatively affect therapeutic outcome by overexpressing pro-survival genes under the control of the hypoxia-inducible factor (HIF). HIF-1 is a heterodimeric transcriptional factor consisting of a regulated alpha (HIF-1α) and a constitutive beta subunit (HIF-1β)...
October 6, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901482/hyperglycemia-triggers-hipk2-protein-degradation
#6
Silvia Baldari, Alessia Garufi, Marisa Granato, Laura Cuomo, Giuseppa Pistritto, Mara Cirone, Gabriella D'Orazi
Homeodomain interacting protein kinase-2 (HIPK2) is an evolutionary conserved kinase that modulates several key molecular pathways to restrain tumor growth and induce p53-depending apoptotic cell-death in response to anticancer therapies. HIPK2 silencing in cancer cells leads to chemoresistance and cancer progression, in part due to p53 inhibition. Recently, hyperglycemia has been shown to reduce p53 phosphorylation at serine 46 (Ser46), the target residue of HIPK2, thus impairing p53 apoptotic function. Here we asked whether hyperglycemia could, upstream of p53, target HIPK2...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27896629/remote-limb-ischemic-preconditioning-protects-rats-against-cerebral-ischemia-via-hif-1%C3%AE-ampk-hsp70-pathway
#7
Ming Xia, Qian Ding, Zhidan Zhang, Qinggen Feng
Remote limb ischemic preconditioning (RIPC) is a clinically feasible strategy to protect against ischemia/reperfusion injury, but the knowledge concerning the mechanism underlying RIPC is scarce. This study was performed to examine the effect of RIPC on brain tissue suffering from ischemia challenge and explore its underlying mechanism in a rat model. The animals were divided into four groups: Sham, middle cerebral artery occlusion (MCAO), RIPC, and MCAO+RIPC. We found that previous exposure to RIPC significantly attenuated neurological dysfunction and lessened brain edema in MCAO+RIPC group...
November 28, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27883071/mint3-apba3-depletion-ameliorates-severe-murine-influenza-pneumonia-and-macrophage-cytokine-production-in-response-to-the-influenza-virus
#8
Takayuki Uematsu, Tomoko Fujita, Hiroki J Nakaoka, Toshiro Hara, Noritada Kobayashi, Yoshinori Murakami, Motoharu Seiki, Takeharu Sakamoto
Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27877208/selection-analysis-and-improvement-of-anti-angiogenesis-compounds-identified-by-an-anti-hif-1%C3%AE-screening-and-validation-system
#9
Chikezie Madu, Liyuan Li, Yi Lu
Cancer cells resort to activating hypoxia-inducible factor-1 (HIF-1) as one of several responses to hypoxic conditions. Overexpression of HIF-1, the transcriptional regulator for a group of malignant-pathway related genes including vascular endothelial growth factor (VEGF), is associated with increased tumor growth, vascularization, and metastasis. HIF-1 is composed of an inducible subunit, HIF-1α and a constitutively expressed subunit, HIF-1ß. HIF-1 activity is mainly dependent on the level of HIF-1α protein, the inducible and regulatory subunit of the HIF-1 heterodimer complex; thus, identification of novel anti-HIF-1α agents will lead to effective blockage of the HIF-1 (HIF-1α)-mediated "switch-on" function for those malignant-pathway related genes and suppression of the HIF-1α/VEGF-mediated signaling pathway that promotes cancer progression and metastasis...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27862498/all-trans-retinoic-acid-preconditioning-enhances-proliferation-angiogenesis-and-migration-of-mesenchymal-stem-cell-in-vitro-and-enhances-wound-repair-in-vivo
#10
M Pourjafar, M Saidijam, K Mansouri, H Ghasemibasir, F Karimi Dermani, R Najafi
OBJECTIVES: Stem cell therapy is considered to be a suitable alternative in treatment of a number of diseases. However, there are challenges in their clinical application in cell therapy, such as to reduce survival and loss of transplanted stem cells. It seems that chemical and pharmacological preconditioning enhances their therapeutic efficacy. In this study, we investigated effects of all-trans retinoic acid (ATRA) on survival, angiogenesis and migration of mesenchymal stem cells (MSCs) in vitro and in a wound-healing model...
November 10, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27858285/the-role-of-hypoxia-inducible-factor-1-in-mild-cognitive-impairment
#11
REVIEW
Osigbemhe Iyalomhe, Sabina Swierczek, Ngozi Enwerem, Yuanxiu Chen, Monica O Adedeji, Joanne Allard, Oyonumo Ntekim, Sheree Johnson, Kakra Hughes, Philip Kurian, Thomas O Obisesan
Neuroinflammation and reactive oxygen species are thought to mediate the pathogenesis of Alzheimer's disease (AD), suggesting that mild cognitive impairment (MCI), a prodromal stage of AD, may be driven by similar insults. Several studies document that hypoxia-inducible factor 1 (HIF-1) is neuroprotective in the setting of neuronal insults, since this transcription factor drives the expression of critical genes that diminish neuronal cell death. HIF-1 facilitates glycolysis and glucose metabolism, thus helping to generate reductive equivalents of NADH/NADPH that counter oxidative stress...
November 17, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27847273/development-of-1-aryl-3-furanyl-thienyl-imidazopyridine-templates-for-inhibitors-against-hypoxia-inducible-factor-hif-1-transcriptional-activity
#12
Shinichiro Fuse, Toshiaki Ohuchi, Yasunobu Asawa, Shinichi Sato, Hiroyuki Nakamura
1,3-Disubstituted-imidazopyridines were designed for developing inhibitors against HIF-1 transcriptional activity. Designed compounds were rapidly synthesized from a key aromatic scaffold via microwave-assisted Suzuki-Miyaura coupling/CH direct arylation sequence. Evaluation of ability to inhibit the hypoxia induced transcriptional activity of HIF-1 revealed that the compound 2i and 3a retained the same level of the inhibitory activity comparing with that of known inhibitor, YC-1 (1). Identified, readily accessible 1-aryl-3-furanyl/thienyl-imidazopyridine templates should be useful for future drug development...
December 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27835695/reference-genes-for-addressing-gene-expression-of-bladder-cancer-cell-models-under-hypoxia-a-step-towards-transcriptomic-studies
#13
Luís Lima, Cristiana Gaiteiro, Andreia Peixoto, Janine Soares, Manuel Neves, Lúcio Lara Santos, José Alexandre Ferreira
Highly aggressive, rapidly growing tumors contain significant areas of hypoxia or anoxia as a consequence of inadequate and/or irregular blood supply. During oxygen deprivation, tumor cells withstand a panoply of adaptive responses, including a shift towards anaerobic metabolism and the reprogramming of the transcriptome. One of the major mediators of the transcriptional hypoxic response is the hypoxia-inducible factor 1 (HIF-1), whose stabilization under hypoxia acts as an oncogenic stimulus contributing to chemotherapy resistance, invasion and metastasis...
2016: PloS One
https://www.readbyqxmd.com/read/27830025/sevoflurane-postconditioning-improves-myocardial-mitochondrial-respiratory-function-and-reduces-myocardial-ischemia-reperfusion-injury-by-up-regulating-hif-1
#14
Long Yang, Peng Xie, Jianjiang Wu, Jin Yu, Tian Yu, Haiying Wang, Jiang Wang, Zhengyuan Xia, Hong Zheng
BACKGROUND: Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27821168/associations-of-proteins-relevant-to-mapk-signaling-pathway-p38mapk-1-hif-1-and-ho-1-with-coronary-lesion-characteristics-and-prognosis-of-peri-menopausal-women
#15
Liqiu Yan, Xufen Cao, Saitian Zeng, Zhe Li, Zheng Lian, Jiawang Wang, Fengfeng Lv, Yunfei Wang, Yanshen Li
BACKGROUND: The present study was intended to explore whether three proteins within MAPK signaling pathway (i.e. p38MAPK-1, HIF-1 and HO-1) were correlated with peri-menopausal women's coronary lesion features and prognosis. METHODS: Altogether 1449 peri-menopausal women were divided into non-coronary artery disease (CAD) group (n = 860) and CAD group (n = 589), including 167 pre-menopausal CAD populations and 422 post-menopausal CAD populations. General information about CAD risk parameters were gathered, including age, family history of CAD or hypertension or diabetes mellitus, bilirubin, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and so on...
November 8, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27814606/regulation-and-function-of-renal-medullary-cyclooxygenase-2-during-high-salt-loading
#16
Tianxin Yang, Mi Liu
Prostaglandins (PGs) are important autocrine/paracrine regulators that contribute to sodium balance and blood pressure control. Along the nephron, the highest amount of PGE2 is found in the distal nephron, an important site for fine-tuning of urinary sodium and water excretion. Cylooxygenase-2 (COX-2) is abundantly expressed in the renal medulla and its expression along with urinary PGE2 excretion is highly induced by chronic salt loading. Factors involved in high salt-induced COX-2 expression in the renal medulla include the hypertonicity, fluid shear stress (FSS), and hypoxia-inducible factor-1 alpha (HIF-1 alpha)...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27811509/molecular-characterization-of-hypoxic-alveolar-epithelial-cells-after-lung-contusion-indicates-an-important-role-for-hif-1%C3%AE
#17
Matthew A Sherman, Madathilparambil V Suresh, Vladislav A Dolgachev, Lane K McCandless, Xiang Xue, Li Ziru, David Machado-Aranda, Yatrik M Shah, Krishnan Raghavendran
OBJECTIVE: To understand the fate and regulation of hypoxic type II alveolar epithelial cells (AECs) after lung contusion (LC). BACKGROUND: LC due to thoracic trauma is a major risk factor for the development of acute respiratory distress syndrome. AECs have recently been implicated as a primary driver of inflammation in LC. The main pathological consequence of LC is hypoxia, and a key mediator of adaptation to hypoxia is hypoxia-inducible factor (HIF)-1. We have recently published that HIF-1α is a major driver of acute inflammation after LC through type II AEC...
November 1, 2016: Annals of Surgery
https://www.readbyqxmd.com/read/27810863/hypoxia-inducible-factor-1%C3%AE-mediates-increased-sympathoexcitation-via-glutamatergic-n-methyl-d-aspartate-receptors-in-the-paraventricular-nucleus-of-rats-with-chronic-heart-failure
#18
Neeru M Sharma, Craig J Cunningham, Hong Zheng, Xuefei Liu, Kaushik P Patel
BACKGROUND: Increased sympathetic outflow is a major contributor to the progression of chronic heart failure (CHF). Potentiation of glutamatergic tone has been causally related to the sympathoexcitation in CHF. Specifically, an increase in the N-methyl-d-aspartate-type 1 receptor (NMDA-NR1) expression within the paraventricular nucleus (PVN) is critically linked to the increased sympathoexcitation during CHF. However, the molecular mechanism(s) for the upregulation of NMDA-NR1 remains unexplored...
November 2016: Circulation. Heart Failure
https://www.readbyqxmd.com/read/27808477/the-roles-of-p300-and-creb-in-high-glucose-induced-hif-1%C3%AE-inactivation-under-hypoxia-condition
#19
Lingtao Ding, Minlie Yang, Tianlan Zhao, Guozhong Lv
INTRODUCTION: Given the high prevalence of diabetes and burning injury worldwide, it is essential to dissect the underlying mechanism of delayed burn wound healing in diabetic subjects, especially the high glucose induced HIF-1-mediated transcription defects. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured with low or high concentrations of glucose. HIF-1α induced VEGF transcription was measured via luciferase assay. Immunofluorescence staining was performed to visualize CREB localization...
November 3, 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27803950/multi-omic-profiling-of-survival-and-metabolic-signaling-networks-in-cells-subjected-to-photodynamic-therapy
#20
Ruud Weijer, Séverine Clavier, Esther A Zaal, Maud M E Pijls, Robert T van Kooten, Klaas Vermaas, René Leen, Aldo Jongejan, Perry D Moerland, Antoine H C van Kampen, André B P van Kuilenburg, Celia R Berkers, Simone Lemeer, Michal Heger
Photodynamic therapy (PDT) is an established palliative treatment for perihilar cholangiocarcinoma that is clinically promising. However, tumors tend to regrow after PDT, which may result from the PDT-induced activation of survival pathways in sublethally afflicted tumor cells. In this study, tumor-comprising cells (i.e., vascular endothelial cells, macrophages, perihilar cholangiocarcinoma cells, and EGFR-overexpressing epidermoid cancer cells) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs)...
November 1, 2016: Cellular and Molecular Life Sciences: CMLS
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