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Lipid membrane disease

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https://www.readbyqxmd.com/read/28544208/ultra-high-field-magnetic-resonance-spectroscopy-in-non-alcoholic-fatty-liver-disease-novel-mechanistic-and-diagnostic-insights-of-energy-metabolism-in-non-alcoholic-steatohepatitis-and-advanced-fibrosis
#1
Stefan Traussnigg, Christian Kienbacher, Martin Gajdošík, Ladislav Valkovič, Emina Halilbasic, Judith Stift, Christian Rechling, Harald Hofer, Petra Steindl-Munda, Peter Ferenci, Fritz Wrba, Siegfried Trattnig, Martin Krššák, Michael Trauner
BACKGROUND & AIMS: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) non-invasive tools obtaining pathomechanistic insights to improve risk stratification are urgently needed. We therefore explored high- and ultra-high-field magnetic resonance spectroscopy (MRS) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of NAFLD. METHODS: MRS and liver biopsy were performed in 30 NAFLD patients with NAFL (n=8) or NASH (n=22)...
April 24, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28544137/phenotypic-identification-of-a-novel-autophagy-inhibitor-chemotype-targeting-lipid-kinase-vps34
#2
Herbert Waldmann, Lucas Robke, Luca Laraia, Marjorie A Carnero Corrales, Georgios Konstantinidis, Makoto Muroi, André Richters, Michael Winzker, Tobias Engbring, Stefano Tomassi, Nobumoto Watanabe, Hiroyuki Osada, Daniel Rauh, Yaowen Wu, Julian Engel
Autophagy is a critical regulator of cellular homeostasis and metabolism. Interference with this process is considered a new approach for the treatment of disease, in particular cancer and neurological disorders. Therefore, novel small molecule autophagy modulators are in high demand. We describe the discovery of autophinib, a potent autophagy inhibitor with a novel chemotype. Autophinib was identified by means of a phenotypic assay monitoring formation of autophagy-induced puncta indicating accumulation of lipidated cytosolic protein LC3 on the autophagosomal membrane...
May 22, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28542792/on-the-complexity-of-clinical-and-molecular-bases-of-neurodegeneration-with-brain-iron-accumulation
#3
REVIEW
Cristina Tello, Alejandra Darling, Vincenzo Lupo, Belén Pérez-Dueñas, Carmen Espinós
Neurodegeneration with brain iron accumulation (NBIA) are a group of inherited heterogeneous neurodegenerative rare disorders. These patients present with dystonia, spasticity, parkinsonism and neuropsychiatric disturbances, along with brain MRI evidence of iron accumulation. In sum, they are devastating disorders and to date, there is no specific treatment. Ten NBIA genes are accepted: PANK2, PLA2G6, C19orf12, COASY, FA2H, ATP13A2, WDR45, FTL, CP, and DCAF17, and. Nonetheless, a relevant percentage of patients remain without genetic diagnosis, suggesting that other novel NBIA genes remain to be discovered...
May 23, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28540446/lipid-per-oxidation-in-mitochondria-an-emerging-target-in-the-ageing-process
#4
REVIEW
O S Ademowo, H K I Dias, D G A Burton, H R Griffiths
Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation...
May 24, 2017: Biogerontology
https://www.readbyqxmd.com/read/28539454/ebola-virus-delta-peptide-is-a-viroporin
#5
Jing He, Lilia I Melnik, Alexander Komin, Gregory Wiedman, Taylor Fuselier, Cameron F Morris, Charles G Starr, Peter C Searson, William R Gallaher, Kalina Hristova, Robert F Garry, William C Wimley
The Ebola virus (EBOV) genome encodes for a partly conserved, 40-residue, nonstructural polypeptide, called the delta peptide, which is produced in abundance during Ebola virus disease. The function of the delta peptide is unknown, but sequence analysis has suggested that delta peptide could be a viroporin, belonging to a diverse family of membrane-permeabilizing small polypeptides involved in replication and pathogenesis of numerous viruses. Full length and conserved C-terminal delta peptide fragments permeabilize the plasma membranes of nucleated cells of rodent, dog, monkey and human origin, increase ion permeability across confluent cell monolayers and permeabilize synthetic lipid bilayers...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28536108/inflammatory-stress-promotes-the-development-of-obesity-related-chronic-kidney-disease-via-cd36-in-mice
#6
Ping Yang, Yayun Xiao, Xuan Luo, Yunfei Zhao, Lei Zhao, Yan Wang, Tingting Wu, Li Wei, Zac Varghese, John F Moorhead, Yaxi Chen, Xiong Z Ruan
Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase CD36. HFD feeding alone resulted in obesity, hyperlipidemia and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression...
May 23, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28535936/lipids-in-infectious-diseases-the-case-of-aids-and-tuberculosis
#7
REVIEW
Fabrice Dumas, Evert Haanappel
Lipids play a central role in many infectious diseases. AIDS (Acquired Immune Deficiency Syndrome) and tuberculosis are two of the deadliest infectious diseases to have struck mankind. The pathogens responsible for these diseases, Human Immunodeficiency Virus-1 and Mycobacterium tuberculosis, rely on lipids and on lipid membrane properties to gain access to their host cells, to persist in them and ultimately to egress from their hosts. In this Review, we discuss the life cycles of these pathogens and the roles played by lipids and membranes...
May 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28535513/pkc-%C3%AE-triggers-egfr-ubiquitination-endocytosis-and-erk-activation-in-podocytes-stimulated-with-high-glucose
#8
Chun-Tao Lei, Yan-Hong Wei, Hui Tang, Qian Wen, Chen Ye, Chun Zhang, Hua Su
BACKGROUND: Protein Kinase C-α (PKC-α) and epidermal growth factor receptor (EGFR) are both involved in diabetic kidney disease; however, the connection between these two proteins during high glucose-induced podocyte injury remains uncertain. METHODS: Diabetes was induced in SD rats by streptozotocin (STZ). Fourteen days later, the kidney cortex was removed and subjected to plasma membrane isolation and lipid raft fractionation. In vitro study human podocyte cell line was differentiated and subjected to various treatments...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28533927/antioxidant-and-anti-inflammatory-medicinal-plants-have-potential-role-in-the-treatment-of-cardiovascular-disease-a-review
#9
REVIEW
Peter Adegbola, Ifewumi Aderibigbe, Wasiu Hammed, Tolulope Omotayo
Cardiovascular disease is a compound name for clusters of disorders afflicting the heart and blood vessels; it is assuming an increasing role as a major cause of morbidity and mortality. Unhealthy practices such as smoking, high intake of saturated fat and cholesterol, diabetes and physical inactivity are predisposing factors. The risk factors cause alteration in vascular integrity, compromised membrane integrity, increase free radical generation and reduced endogenous antioxidant system resulting in oxidative stress...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28533146/bioactive-lipids-derived-from-arachidonic-acid-metabolism-in-different-types-of-renal-replacement-therapy
#10
Joanna Stępniewska, Barbara Dołęgowska, Kamila Puchałowicz, Edyta Gołembiewska, Kazimierz Ciechanowski
INTRODUCTION: Metabolism and plasma concentration of lipids and lipid-derived compounds play an important role in kidney physiology and pathological processes. The component of membrane phospholipids - arachidonic acid (AA) and its active derivatives - eicosanoids are involved in the development of hypertension, diabetes, inflammation and may contribute to progression of chronic kidney disease (CKD). The purpose of the study was to determine, whether the type of renal replacement therapy has an effect on eicosanoids metabolism...
May 19, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28532702/trimetazidine-in-the-prevention-of-contrast-induced-nephropathy-in-chronic-kidney-disease
#11
Tarek A Ibrahim, Ramzy H El-Mawardy, Ahmed S El-Serafy, Ehab M El-Fekky
BACKGROUND: Contrast induced nephropathy (CIN) may be defined as Acute Renal Failure (ARF) that occurs within 24-72h of exposure to intra-venous or intra-arterial iodinated contrast media that cannot be attributed to other causes. CIN occurs in up to 5% of hospitalized patients with normal renal function prior to injection of contrast media. It occurs more frequently in patients with renal impairment particularly if associated with diabetic nephropathy. Among all procedures utilizing contrast agents for either diagnostic or therapeutic purposes, coronary angiography and percutaneous coronary interventions are associated with the highest rates of CIN...
February 10, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28532689/lipid-composition-of-microdomains-is-altered-in-neuronopathic-gaucher-disease-sheep-brain-and-spleen
#12
Leanne K Hein, Tina Rozaklis, Melissa K Adams, John J Hopwood, Litsa Karageorgos
Gaucher disease is a lysosomal storage disorder caused by a deficiency in glucocerebrosidase activity that leads to accumulation of glucosylceramide and glucosylsphingosine. Membrane raft microdomains are discrete, highly organized microdomains with a unique lipid composition that provide the necessary environment for specific protein-lipid and protein-protein interactions to take place. In this study we purified detergent resistant membranes (DRM; membrane rafts) from the occipital cortex and spleen from sheep affected with acute neuronopathic Gaucher disease and wild-type controls...
May 17, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28531236/psychosine-enhances-the-shedding-of-membrane-microvesicles-implications-in-demyelination-in-krabbe-s-disease
#13
Ludovic D'Auria, Cory Reiter, Emma Ward, Ana Lis Moyano, Michael S Marshall, Duc Nguyen, Giuseppe Scesa, Zane Hauck, Richard van Breemen, Maria I Givogri, Ernesto R Bongarzone
In prior studies, our laboratory showed that psychosine accumulates and disrupts lipid rafts in brain membranes of Krabbe's disease. A model of lipid raft disruption helped explaining psychosine's effects on several signaling pathways important for oligodendrocyte survival and differentiation but provided more limited insight in how this sphingolipid caused demyelination. Here, we have studied how this cationic inverted coned lipid affects the fluidity, stability and structure of myelin and plasma membranes...
2017: PloS One
https://www.readbyqxmd.com/read/28528666/role-of-nonneuronal-trpv4-signaling-in-inflammatory-processes
#14
Pradeep Rajasekhar, Daniel P Poole, Nicholas A Veldhuis
Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28527668/imaging-mass-spectrometry-ims-of-cortical-lipids-from-preclinical-to-severe-stages-of-alzheimer-s-disease
#15
E Gónzalez de San Román, I Manuel, M T Giralt, I Ferrer, R Rodríguez-Puertas
Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting millions of patients worldwide. Previous studies have demonstrated alterations in the lipid composition of lipid extracts from plasma and brain samples of AD patients. However, there is no consensus regarding the qualitative and quantitative changes of lipids in brains from AD patients. In addition, the recent developments in imaging mass spectrometry methods are leading to a new stage in the in situ analysis of lipid species in brain tissue slices from human postmortem samples...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28526873/role-of-s-palmitoylation-by-zdhhc13-in-mitochondrial-function-and-metabolism-in-liver
#16
Li-Fen Shen, Yi-Ju Chen, Kai-Ming Liu, Amir N Saleem Haddad, I-Wen Song, Hsiao-Yuh Roan, Li-Ying Chen, Jeffrey J Y Yen, Yu-Ju Chen, Jer-Yuarn Wu, Yuan-Tsong Chen
Palmitoyltransferase (PAT) catalyses protein S-palmitoylation which adds 16-carbon palmitate to specific cysteines and contributes to various biological functions. We previously reported that in mice, deficiency of Zdhhc13, a member of the PAT family, causes severe phenotypes including amyloidosis, alopecia, and osteoporosis. Here, we show that Zdhhc13 deficiency results in abnormal liver function, lipid abnormalities, and hypermetabolism. To elucidate the molecular mechanisms underlying these disease phenotypes, we applied a site-specific quantitative approach integrating an alkylating resin-assisted capture and mass spectrometry-based label-free strategy for studying the liver S-palmitoylome...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28523433/structural-and-functional-roles-of-ether-lipids
#17
REVIEW
John M Dean, Irfan J Lodhi
Ether lipids, such as plasmalogens, are peroxisome-derived glycerophospholipids in which the hydrocarbon chain at the sn-1 position of the glycerol backbone is attached by an ether bond, as opposed to an ester bond in the more common diacyl phospholipids. This seemingly simple biochemical change has profound structural and functional implications. Notably, the tendency of ether lipids to form non-lamellar inverted hexagonal structures in model membranes suggests that they have a role in facilitating membrane fusion processes...
May 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28521874/sirna-mediated-inhibition-of-srebp-cleavage-activating-protein-reduces-dyslipidemia-in-spontaneously-dysmetabolic-rhesus-monkeys
#18
Beth Ann Murphy, Marija Tadin-Strapps, Kristian Jensen, Robin Mogg, Andy Liaw, Kithsiri Herath, Gowri Bhat, David G McLaren, Stephen F Previs, Shirly Pinto
BACKGROUND: SREBP cleavage-activating protein (SCAP) is a cholesterol binding endoplasmic reticulum (ER) membrane protein that is required to activate SREBP transcription factors. SREBPs regulate genes involved in lipid biosynthesis. They also influence lipid clearance by modulating the expression of LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Inhibiting SCAP decreases circulating PCSK9, triglycerides (TG), and LDL-cholesterol (LDL-C), both in vitro and in vivo...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28521611/sgpl1-sphingosine-phosphate-lyase-1-modulates-neuronal-autophagy-via-phosphatidylethanolamine-production
#19
Daniel N Mitroi, Indulekha Karunakaran, Markus Gräler, Julie D Saba, Dan Ehninger, María Dolores Ledesma, Gerhild van Echten-Deckert
Macroautophagy/autophagy defects have been identified as critical factors underlying the pathogenesis of neurodegenerative diseases. The roles of the bioactive signaling lipid sphingosine-1-phosphate (S1P) and its catabolic enzyme SGPL1/SPL (sphingosine phosphate lyase 1) in autophagy are increasingly recognized. Here we provide in vitro and in vivo evidence for a previously unidentified route through which SGPL1 modulates autophagy in neurons. SGPL1 cleaves S1P into ethanolamine phosphate, which is directed toward the synthesis of phosphatidylethanolamine (PE) that anchors LC3-I to phagophore membranes in the form of LC3-II...
May 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28518475/lipid-bodies-accumulation-in-leishmania-infantum-infected-c57bl-6-macrophages
#20
Nilda E Rodríguez, Ryan D Lockard, Elizabeth A Turcotte, Théo Araujo-Santos, Patrícia T Bozza, Valéria M Borges, Mary E Wilson
Lipid bodies (LBs) are intracellular accumulations of neutral lipids surrounded by a single membrane. These organelles are involved in the production of eicosanoids, which modulate immunity by either promoting or dampening inflammatory responses. Leishmania infantum, the etiological agent of visceral leishmaniasis in Brazil, is an intracellular parasite that causes disease by suppressing macrophage microbicidal responses. C57BL/6 mouse bone marrow-derived macrophages infected with L. infantum strain LcJ had higher numbers of LB+ cells (P<0...
May 18, 2017: Parasite Immunology
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