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FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology

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https://www.readbyqxmd.com/read/28646018/the-amyloid-precursor-protein-modulates-%C3%AE-2a-adrenergic-receptor-endocytosis-and-signaling-through-disrupting-arrestin-3-recruitment
#1
Fang Zhang, Mary Gannon, Yunjia Chen, Lufang Zhou, Kai Jiao, Qin Wang
The amyloid precursor protein (APP) has long been appreciated for its role in Alzheimer's disease (AD) pathology. However, less is known about the physiologic function of APP outside of AD. Particularly, whether and how APP may regulate functions of cell surface receptors, including GPCRs, remains largely unclear. In this study, we identified a novel direct interaction between APP and the α2A adrenergic receptor (α2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with α2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28646017/ror%C3%AE-modulates-semaphorin-3e-transcription-and-neurovascular-interaction-in-pathological-retinal-angiogenesis
#2
Ye Sun, Chi-Hsiu Liu, Zhongxiao Wang, Steven S Meng, Samuel B Burnim, John Paul SanGiovanni, Theodore M Kamenecka, Laura A Solt, Jing Chen
Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28646016/tshb-mrna-is-linked-to-cholesterol-metabolism-in-adipose-tissue
#3
José María Moreno-Navarrete, María Moreno, Francisco Ortega, Gemma Xifra, Shangyu Hong, John M Asara, José C E Serrano, Mariona Jové, Pavlos Pissios, Matthias Blüher, Wifredo Ricart, Manuel Portero-Otin, José Manuel Fernández-Real
Subclinical hypothyroidism is known to be associated with increased serum cholesterol. Since thyroid-stimulating hormone (TSH) exerts an inductor effect on cholesterol biosynthesis, we aimed to investigate the relationship between TSH mRNA and cholesterol metabolism in human adipose tissue (AT). Cross-sectionally, AT TSH-β (TSHB) mRNA was evaluated in 4 independent cohorts in association with serum total and LDL cholesterol, and AT lipidomics. Longitudinally, the effects of statins and of diet and exercise on AT TSHB mRNA were also examined...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28642328/leukocyte-diversity-in-resolving-and-nonresolving-mechanisms-of-cardiac-remodeling
#4
REVIEW
Bochra Tourki, Ganesh Halade
In response to myocardial infarction (MI), time-dependent leukocyte infiltration is critical to program the acute inflammatory response. Post-MI leukocyte density, residence time in the infarcted area, and exit from the infarcted injury predict resolving or nonresolving inflammation. Overactive or unresolved inflammation is the primary determinant in heart failure pathology post-MI. Here, our review describes supporting evidence that the acute inflammatory response also guides the generation of healing and regenerative mediators after cardiac damage...
June 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28642327/declining-histone-acetyltransferase-gcn5-represses-bmsc-mediated-angiogenesis-during-osteoporosis
#5
Huan Jing, Li Liao, Xiaoxia Su, Yi Shuai, Xinjing Zhang, Zhihong Deng, Yan Jin
Angiogenesis is disrupted in age-related and postmenopausal osteoporosis. However, the mechanisms of the disorder remain elusive. We confirmed in this study that, in accordance with the decrease of H-type vessels, the proangiogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) declined during osteoporosis. Screening of the histone acetyltransferase family revealed that GCN5 decreased in BMSCs derived from osteoporotic femur. Further analysis identified that GCN5 plays important roles in regulating the proangiogenic potential of BMSCs...
June 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28637652/gm-csf-and-m-csf-primed-m%C3%AF-s-present-similar-resolving-but-distinct-inflammatory-lipid-mediator-signatures
#6
Ana Lukic, Pia Larssen, Alexander Fauland, Bengt Samuelsson, Craig E Wheelock, Susanne Gabrielsson, Olof Radmark
M1 and M2 activated Mϕs have different roles in inflammation. Because pathogens may first encounter resting cells, we investigated lipid mediator profiles prior to full activation. Human monocytes were differentiated with granulocyte Mϕ colony-stimulating factor (GM-CSF) or Mϕ colony-stimulating factor (M-CSF), which are known to prime toward M1 or M2 phenotypes, respectively. Lipid mediators released during resting conditions and produced in response to bacterial stimuli (LPS/N-formylmethionyl-leucyl-phenylalanine or peptidoglycan) were quantified by liquid chromatography-mass spectrometry...
June 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28634213/omega-3-fatty-acids-increase-the-unfolded-protein-response-and-improve-amyloid-%C3%AE-phagocytosis-by-macrophages-of-patients-with-mild-cognitive-impairment
#7
Henry M Olivera-Perez, Larry Lam, Johnny Dang, Weilan Jiang, Fabian Rodriguez, Elizabeth Rigali, Sarah Weitzman, Verna Porter, Liudmilla Rubi, Marco Morselli, Matteo Pellegrini, Milan Fiala
Mϕs of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. ω-3 in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28634212/prolonged-darkness-reduces-liver-fibrosis-in-a-mouse-model-of-primary-sclerosing-cholangitis-by-mir-200b-down-regulation
#8
Nan Wu, Fanyin Meng, Tianhao Zhou, Yuyan Han, Lindsey Kennedy, Julie Venter, Heather Francis, Sharon DeMorrow, Paolo Onori, Pietro Invernizzi, Francesca Bernuzzi, Romina Mancinelli, Eugenio Gaudio, Antonio Franchitto, Shannon Glaser, Gianfranco Alpini
Melatonin therapy or prolonged exposure to complete darkness reduces biliary hyperplasia and liver fibrosis in bile-duct-ligated (BDL) rats; however, no information exists in primary sclerosing cholangitis (PSC). Thus, we aimed to determine the therapeutic effects of prolonged dark therapy or melatonin administration on hepatic fibrosis in the Mdr2(-/-) mouse model of PSC. Melatonin levels, biliary mass, liver fibrosis, angiogenesis and miR-200b expression were evaluated in wild-type and Mdr2(-/-) mice exposed to darkness or melatonin treatment or in male PSC patient samples and healthy controls...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28626028/excess-centrosomes-induce-p53-dependent-senescence-without-dna-damage-in-endothelial-cells
#9
Zhixian Yu, Dana L Ruter, Erich J Kushner, Victoria L Bautch
Tumor blood vessels support tumor growth and progression. Centrosomes are microtubule organization centers in cells, and often up to 30% of tumor endothelial cells (ECs) acquire excess (>2) centrosomes. Although excess centrosomes can lead to aneuploidy and chromosome instability in tumor cells, how untransformed ECs respond to excess centrosomes is poorly understood. We found that the frequency of primary human ECs with excess centrosomes was quickly reduced in a p53-dependent manner. Excess centrosomes in ECs were associated with p53 phosphorylation at Ser33, increased p21 levels, and decreased cell proliferation and expression of senescence markers, but independent of DNA damage and apoptosis...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28626027/selective-activation-of-epidermal-growth-factor-receptor-in-renal-proximal-tubule-induces-tubulointerstitial-fibrosis
#10
Jessica M Overstreet, Yinqiu Wang, Xin Wang, Aolei Niu, Leslie S Gewin, Bing Yao, Raymond C Harris, Ming-Zhi Zhang
Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of diabetic nephropathy and renal fibrosis; however, the causative role of sustained EGFR activation is unclear. Here, we generated a novel kidney fibrotic mouse model of persistent EGFR activation by selectively expressing the EGFR ligand, human heparin-binding EGF-like growth factor (HB-EGF), in renal proximal tubule epithelium. Human HB-EGF expression increased tyrosine kinase phosphorylation of EGFR and the subsequent activation of downstream signaling pathways, including ERK and AKT, as well as the profibrotic TGF-β1/SMAD pathway...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28626026/protein-kinase-c%C3%AE-activates-fat-mass-and-obesity-associated-protein-by-influencing-its-ubiquitin-proteasome-degradation
#11
Haoran Tai, Xiaobo Wang, Jiao Zhou, Xiaojuan Han, Tingting Fang, Hui Gong, Ning Huang, Honghan Chen, Jianqiong Qin, Ming Yang, Xiawei Wei, Li Yang, Hengyi Xiao
PKCβ is a serine-threonine kinase associated with obesity and diabetic complications; its activation contributes to weight gain, and deletion of its gene results in resistance to genetic- and diet-induced obesity. Fat mass and obesity-associated (FTO) protein is a recently identified RNA demethylase, and its overexpression in mice leads to increased body weight as well as fat mass. Although sharing some features in anabolism regulation, PKCβ and FTO have not been investigated together; therefore, their relationship has not been established...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28626025/intranasal-administration-of-mesenchymoangioblast-derived-mesenchymal-stem-cells-abrogates-airway-fibrosis-and-airway-hyperresponsiveness-associated-with-chronic-allergic-airways-disease
#12
Simon G Royce, Siddharth Rele, Brad R S Broughton, Kilian Kelly, Chrishan S Samuel
Structural changes known as airway remodeling (AWR) characterize chronic/severe asthma and contribute to lung dysfunction. Thus, we assessed the in vivo efficacy of induced pluripotent stem cell and mesenchymoangioblast-derived mesenchymal stem cells (MCA-MSCs) on AWR in a murine model of chronic allergic airways disease (AAD)/asthma. Female Balb/c mice were subjected to a 9-wk model of ovalbumin (OVA)-induced chronic AAD and treated intravenously or intranasally with MCA-MSCs from weeks 9 to11. Changes in airway inflammation (AI), AWR, and airway hyperresponsiveness (AHR) were assessed...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28626024/intersectin-2-controls-actin-cap-formation-and-meiotic-division-in-mouse-oocytes-through-the-cdc42-pathway
#13
Jiaqi Zhang, Rujun Ma, Ling Li, Lina Wang, Xiaojing Hou, Longsen Han, Juan Ge, Mo Li, Qiang Wang
Intersectins (ITSNs), an evolutionarily conserved adaptor protein family, have been implicated in multiple biologic processes; however, their functions in mammalian oocytes have not been addressed. Here, we report delayed meiotic resumption and defective cytokinesis upon specific depletion of ITSN2 in mouse oocytes. In particular, abnormal spindle, misaligned chromosomes, and loss of cortical actin cap are readily observed in ITSN2-depleted oocytes. Similarly, a small molecule that targets the Cdc42-ITSN interaction also disrupts oocyte maturation and actin polymerization...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28619712/targeting-acetylcholine-receptor-m3-prevents-the-progression-of-airway-hyperreactivity-in-a-mouse-model-of-childhood-asthma
#14
Kruti R Patel, Yan Bai, Kenneth G Trieu, Juliana Barrios, Xingbin Ai
Asthma often progresses into adulthood from early-life episodes of adverse environmental exposures. However, how the injury to developing lungs contributes to the pathophysiology of persistent asthma remains poorly understood. In this study, we identified an age-related mechanism along the cholinergic nerve-airway smooth muscle (ASM) axis that underlies prolonged airway hyperreactivity (AHR) in mice. We showed that ASM continued to mature until ∼3 wk after birth. Coinciding with postnatal ASM maturation, there was a critical time window for the development of ASM hypercontractility after cholinergic stimulation...
June 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28615326/prenatal-nicotinic-exposure-prolongs-superior-laryngeal-c-fiber-mediated-apnea-and-bradycardia-through-enhancing-neuronal-trpv1-expression-and-excitation
#15
Xiuping Gao, Lei Zhao, Jianguo Zhuang, Na Zang, Fadi Xu
Maternal cigarette smoke, including prenatal nicotinic exposure (PNE), is responsible for sudden infant death syndrome (SIDS). The fatal events of SIDS are characterized by severe bradycardia and life-threatening apneas. Although activation of transient receptor potential vanilloid 1 (TRPV1) of superior laryngeal C-fibers (SLCFs) could induce bradycardia and apnea and has been implicated in SIDS pathogenesis, how PNE affects the SLCF-mediated cardiorespiratory responses remains unexplored. Here, we tested the hypothesis that PNE would aggravate the SLCF-mediated apnea and bradycardia via up-regulating TRPV1 expression and excitation of laryngeal C-neurons in the nodose/jugular (N/J) ganglia...
June 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28615325/calcium-calmodulin-dependent-protein-kinase-regulates-the-pink1-parkin-and-dj-1-pathways-of-mitophagy-during-sepsis
#16
Xianghong Zhang, Du Yuan, Qian Sun, Li Xu, Emma Lee, Anthony J Lewis, Brian S Zuckerbraun, Matthew R Rosengart
During sepsis and shock states, mitochondrial dysfunction occurs. Consequently, adaptive mechanisms, such as fission, fusion, and mitophagy, are induced to eliminate damaged portions or entire dysfunctional mitochondria. The regulatory PINK1/Parkin and DJ-1 pathways are strongly induced by mitochondrial depolarization, although a direct link between loss of mitochondrial membrane potential (ΔΨ) and mitophagy has not been identified. Mitochondria also buffer Ca(2+), and their buffering capacity is dependent on ΔΨ...
June 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28611114/notch1-deficiency-in-postnatal-neural-progenitor-cells-in-the-dentate-gyrus-leads-to-emotional-and-cognitive-impairment
#17
Shufang Feng, Tianyao Shi, Jiangxia Qiu, Haihong Yang, Yan Wu, Wenxia Zhou, Wei Wang, Haitao Wu
It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in hippocampal mature neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus...
June 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28596235/epidermal-growth-factor-induced-pyruvate-dehydrogenase-kinase-1-expression-enhances-head-and-neck-squamous-cell-carcinoma-metastasis-via-up-regulation-of-fibronectin
#18
Jinn-Yuan Hsu, Jang-Yang Chang, Kwang-Yu Chang, Wen-Chang Chang, Ben-Kuen Chen
Epidermal growth factor receptor (EGFR) activation is a major cause of metastasis in such cancers as head and neck squamous cell carcinoma (HNSCC); however, whether the metabolic enzyme, pyruvate dehydrogenase kinase 1 (PDK1), mediates EGF-enhanced HNSCC metastasis remains unclear. Of interest, we found that EGF induced PDK1 expression in HNSCC. Tumor cell transformation induced by EGF was repressed by PDK1 knockdown, and the down-regulation of PDK1 expression or inhibition of its activity significantly blocked EGF-enhanced cell migration and invasion...
June 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28596234/cathepsin-b-as-a-potential-cystatin-m-e-target-in-the-mouse-hair-follicle
#19
Merel A W Oortveld, Ivonne M J J van Vlijmen-Willems, Ferry F J Kersten, Tsing Cheng, Martijn Verdoes, Piet E J van Erp, Sjef Verbeek, Thomas Reinheckel, Wiljan J A J Hendriks, Joost Schalkwijk, Patrick L J M Zeeuwen
Deficiency of the cysteine protease inhibitor cystatin M/E (Cst6) in mice leads to disturbed epidermal cornification, impaired barrier function, and neonatal lethality. We report the rescue of the lethal skin phenotype of ichq (Cst6-deficient; Cst6(-/-)) mice by transgenic, epidermis-specific, reexpression of Cst6 under control of the human involucrin (INV) promoter. Rescued Tg(INV-Cst6)Cst6(ichq/ichq) mice survive the neonatal phase, but display severe eye pathology and alopecia after 4 mo. We observed keratitis and squamous metaplasia of the corneal epithelium, comparable to Cst6(-/-)Ctsl(+/-) mice, as we have reported in other studies...
June 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28596233/adaptable-interaction-between-aquaporin-1-and-band-3-reveals-a-potential-role-of-water-channel-in-blood-co2-transport
#20
Kate Hsu, Ting-Ying Lee, Ammasi Periasamy, Fu-Jen Kao, Li-Tzu Li, Chuang-Yu Lin, Hui-Ju Lin, Marie Lin
Human CO2 respiration requires rapid conversion between CO2 and HCO3(-) Carbonic anhydrase II facilitates this reversible reaction inside red blood cells, and band 3 [anion exchange (AE)-1] provides a passage for HCO3(-) flux across the cell membrane. These 2 proteins are core components of the CO2 transport metabolon. Intracellular H2O is necessary for CO2/HCO3(-) conversion. However, abundantly expressed aquaporin (AQP)-1 in erythrocytes is thought not to be part of band 3 complexes or the CO2 transport metabolon...
June 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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