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Lipid mediators

Wenjia Lou, Hsiu-Chi Ting, Christian jA Reynolds, Yulia Y Tyurina, Vladimir A Tyurin, Yiran Li, Jiajia Ji, Wenxi Yu, Zhuqing Liang, Detcho A Stoyanovsky, Tamil S Anthonymuthu, Michael A Frasso, Peter Wipf, Joel S Greenberger, Hülya Bayir, Valerian E Kagan, Miriam L Greenberg
Cardiolipin (CL) is a unique phospholipid localized almost exclusively within the mitochondrial membranes where it is synthesized. Newly synthesized CL undergoes acyl remodeling to produce CL species enriched with unsaturated acyl groups. Cld1 is the only identified CL specific phospholipase in yeast and is required to initiate the CL remodeling pathway. In higher eukaryotes, peroxidation of CL, yielding CLOX , has been implicated in the cellular signaling events that initiate apoptosis. CLOX can undergo enzymatic hydrolysis, resulting in the release of lipid mediators with signaling properties...
June 20, 2018: Biochimica et Biophysica Acta
Peiyi Liu, Hongkun Lin, Yanyan Xu, Feng Zhou, Jing Wang, Jingjing Liu, Xinhong Zhu, Xiaoping Guo, Yuhan Tang, Ping Yao
SCOPE: Naturally occurring quercetin has been found to induce mitophagy and prevent non-alcoholic fatty liver disease (NAFLD). However, it still remains elusive whether frataxin upregulation by quercetin contributes to the beneficial effect through mitophagy or not. METHODS AND RESULTS: Adult male C57BL/J mice were fed a high fat diet (HFD, 60% of energy from fat) with quercetin (100 mg/ or not for 10 weeks. Quercetin alleviated HFD-induced histopathological changes, disorders of lipid metabolism, mitochondrial damage...
June 23, 2018: Molecular Nutrition & Food Research
Jennifer K Colby, Jonathan Jaoude, Fuyao Liu, Imad Shureiqi
Polyunsaturated fatty acids (PUFAs) are enzymatically converted to a variety of bioactive products through insertion of molecular oxygen. PUFA-derived mediators can have either inflammatory or anti-inflammatory/pro-resolving properties, depending upon their specific structures. The relative harm or benefit of these mediators can also be tissue and context dependent. These mediators play important roles in maintaining homeostasis and their dysregulation is involved in pathogenesis of cancers, especially those associated with chronic inflammation...
June 22, 2018: Cancer Metastasis Reviews
Li Xue, Xueyi Li, Qingping Chen, Juntao He, Yanying Dong, Jing Wang, Siyao Shen, Rui Jia, Quan Jin Zang, Ting Zhang, Ming Li, Yan Geng
Dopamine D3 receptor (D3R) on immune cells is involved in the pathogenesis of rheumatoid arthritis (RA). Mast cells (MCs) are currently identified as important effector cells in synovial inflammation of RA, but little is known about the role of D3R on synovial MCs in the pathogenesis of RA. Several inflammatory cells in the synovium induce reactive oxygen species (ROS) formation which are involved in the progression of RA. However, it is unclear whether D3R on synovial MCs is related to the levels of ROS in RA patients...
June 22, 2018: Clinical Rheumatology
Jinmi Lee, Seok-Woo Hong, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee
Lipin-1 performs dual function during lipid metabolism, i.e., it functions as a transcriptional coactivator and as a phosphatidate phosphatase during triglyceride biosynthesis. We investigated whether exendin-4 prevented endoplasmic reticulum (ER) stress-induced hepatic steatosis and whether the protective effects of exendin-4 were associated with lipin-1 signaling. Tunicamycin and thapsigargin, ER stress inducers, increased triglycerides (TG) content and expression of genes encoding lipid droplet surface proteins...
June 22, 2018: Cell Stress & Chaperones
Liming Wang, Yik-Lam Cho, Yancheng Tang, Jigang Wang, Jung-Eun Park, Yajun Wu, Chunxin Wang, Yan Tong, Ritu Chawla, Jianbin Zhang, Yin Shi, Shuo Deng, Guang Lu, Yihua Wu, Hayden Weng-Siong Tan, Pornteera Pawijit, Grace Gui-Yin Lim, Hui-Ying Chan, Jingzi Zhang, Lei Fang, Hanry Yu, Yih-Cherng Liou, Mallilankaraman Karthik, Boon-Huat Bay, Kah-Leong Lim, Siu-Kwan Sze, Celestial T Yap, Han-Ming Shen
Mitophagy is an important type of selective autophagy for specific elimination of damaged mitochondria. PTEN-induced putative kinase protein 1 (PINK1)-catalyzed phosphorylation of ubiquitin (Ub) plays a critical role in the onset of PINK1-Parkin-mediated mitophagy. Phosphatase and tensin homolog (PTEN)-long (PTEN-L) is a newly identified isoform of PTEN, with addition of 173 amino acids to its N-terminus. Here we report that PTEN-L is a novel negative regulator of mitophagy via its protein phosphatase activity against phosphorylated ubiquitin...
June 22, 2018: Cell Research
Jayne F Martin Carli, Charles A LeDuc, Yiying Zhang, George Stratigopoulos, Rudolph L Leibel
SNPs in the first intron of FTO convey effects on adiposity by mechanisms that remain unclear, but appear to include modulation of expression of FTO itself, as well as other genes in cis. FTO expression is lower in fibroblasts and iPSC-derived neurons of individuals segregating for FTO obesity risk alleles. We employed in vitro adipogenesis models to investigate molecular mechanisms by which Fto affects adipocyte development and function. Fto expression is upregulated during adipogenesis, and is required for the maintenance of CEBPB and Cebpd / CEBPD expression in murine and human adipocytes in vitro Fto knockdown decreases both the number of 3T3-L1 cells that differentiate into adipocytes as well as the amount of lipid per mature adipocyte...
June 22, 2018: Journal of Lipid Research
Caitlin W Brown, John J Amante, Arthur M Mercurio
Ferroptosis is an iron-dependent form of programmed cell death characterized by the accumulation of lipid-targeting reactive oxygen species that kill cells by damaging their plasma membrane. The lipid-repair enzyme glutathione peroxidase 4 (GPX4) protects against this oxidative damage and enables cells to resist ferroptosis. Recent work has revealed that matrix-detached carcinoma cells can be susceptible to ferroptosis and that they can evade this fate through the signaling properties of the α6β4 integrin, which sustains GPX4 expression...
June 22, 2018: Journal of Biological Chemistry
Eli Fernández-de Gortari, L Michel Espinoza-Fonseca
Sarcoplasmic reticulum Ca2+ -ATPase (SERCA) is critical for cardiac Ca2+ transport. Reversal of phospholamban (PLB)-mediated SERCA inhibition by saturating Ca2+ conditions operates as a physiological rheostat to reactivate SERCA function in the absence of PLB phosphorylation. Here, we performed extensive atomistic molecular dynamics simulations to probe the structural mechanism of this process. Simulation of the inhibitory complex at super-physiological Ca2+ concentrations ([Ca2+ ] = 10 mM) revealed that Ca2+ ions interact primarily with SERCA and the lipid headgroups, but not with PLB's cytosolic domain or the cytosolic side of the SERCA-PLB interface...
June 22, 2018: Journal of Biological Chemistry
Sindhu Ramesh, Manoj Govindarajulu, Vishnu Suppiramaniam, Timothy Moore, Muralikrishnan Dhanasekaran
The brain contains various forms of lipids that are important for maintaining its structural integrity and regulating various signaling cascades. Autotaxin (ATX) is an ecto-nucleotide pyrophosphatase/phosphodiesterase-2 enzyme that hydrolyzes extracellular lysophospholipids into the lipid mediator lysophosphatidic acid (LPA). LPA is a major bioactive lipid which acts through G protein-coupled receptors (GPCRs) and plays an important role in mediating cellular signaling processes. The majority of synthesized LPA is derived from membrane phospholipids through the action of the secreted enzyme ATX...
June 21, 2018: International Journal of Molecular Sciences
Nicolas Henry, Eva-Maria Krammer, Florian Stengel, Quentin Adams, François Van Liefferinge, Ellen Hubin, Rui Chaves, Rouslan Efremov, Ruedi Aebersold, Guy Vandenbussche, Martine Prévost, Vincent Raussens, Stéphanie Deroo
Apolipoprotein E (apoE) is a forefront actor in the transport of lipids and the maintenance of cholesterol homeostasis, and is also strongly implicated in Alzheimer's disease. Upon lipid-binding apoE adopts a conformational state that mediates the receptor-induced internalization of lipoproteins. Due to its inherent structural dynamics and the presence of lipids, the structure of the biologically active apoE remains so far poorly described. To address this issue, we developed an innovative hybrid method combining experimental data with molecular modeling and dynamics to generate comprehensive models of the lipidated apoE4 isoform...
June 22, 2018: PLoS Computational Biology
Isabel Forner-Piquer, Constantinos C Mylonas, Josep Calduch-Giner, Francesca Maradonna, Giorgia Gioacchini, Marco Allarà, Fabiana Piscitelli, Vincenzo Di Marzo, Jaume Pérez-Sánchez, Oliana Carnevali
The increasing manufacture of plastics and their mismanagement has turned plastic into a ubiquitous waste in the marine environment. Among all the substances conforming the plastic items, the effects of a dietary Bisphenol A (BPA) and Di-isononyl phthalate (DiNP) have been evaluated in adult male gilthead sea bream, focusing on their effects in the modulation of the Endocannabinoid System (ECS). In zebrafish, the ECS has been recently chosen as a new target for the activity of some Endocrine Disrupting Chemicals (EDC), since it represents a complex lipid signaling network essential for the well-being of the organisms...
June 19, 2018: Environment International
Aike Jeucken, J Bernd Helms, Jos F Brouwers
E. coli has three Cls-isoenzymes for cardiolipin (CL) synthesis but the differences between these three enzymes remain unresolved. All three Cls enzymes contain the phospholipase D (PLD) characteristic HKD motive and synthesize CL using PLD activity. Here, using LC-MS we show the effect of overexpressing or deletion of the three individual Cls enzymes on the lipidome, which included changes in lipid class distribution and CL species profiles. We demonstrate, for the first time, that overexpression of only ClsB resulted in the appreciable synthesis of a variety of phosphatidylalcohols, thereby establishing a 'classic' PLD activity for this enzyme: phospholipid headgroup exchange...
June 19, 2018: Biochimica et Biophysica Acta
Vittoria Massafra, Roberto Pellicciari, Antimo Gioiello, Saskia W C van Mil
Bile acids are amphipathic molecules that were previously known to serve as fat solubilizers in the intestine in postprandial conditions. In the last two decades, bile acids have been recognized as signaling molecules regulating energy metabolism pathways via, amongst others, the farnesoid X receptor (FXR). Upon bile acid activation, FXR controls expression of genes involved in bile acid, lipid, glucose and amino acid metabolism. In addition, FXR activation has been shown to limit the inflammatory response...
June 19, 2018: Pharmacology & Therapeutics
Karolina Serhan, Allison Gartung, Dipak Panigrahy
Ovarian cancer is the most lethal gynecologic malignancy among women. Due to the heterogeneity and complexity of the disease, as well as the insidious onset of symptoms, timely diagnosis remains extremely challenging. Despite recent advances in chemotherapy regimens for ovarian cancer patients, many still suffer from recurrence and ultimately succumb to the disease; thus, there is an urgent need for the identification of novel therapeutic targets. Within this rapidly evolving field, the role of platelets in the ovarian cancer tumor microenvironment has garnered increased attention...
June 19, 2018: Prostaglandins & Other Lipid Mediators
Alexandra Yu Antipina, Andrey A Gurtovenko
Liposome carriers for delivering small interfering RNA (siRNA) into target cells are of tremendous importance because the siRNA-based therapy offers a completely new approach for treating a wide range of diseases, including cancer and viral infections. In this paper we employ the state-of-the-art computer simulations to get an atomic-scale insight into the interactions of siRNA with zwitterionic (neutral) lipids. Our computational findings clearly demonstrate that siRNA does adsorb on the surface of a neutral lipid bilayer...
June 22, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Anu Paul, Vered Padler-Karavani
All living cells are covered with a dense "sugar-coat" of carbohydrate chains (glycans) conjugated to proteins and lipids. The cell surface glycome is determined by a non-template driven process related to the collection of enzymes that assemble glycans in a sequential manner. In mammals, many of these glycans are topped with sialic acids (Sia), a large family of acidic sugars. The "Sialome" is highly diverse owing to various Sia types, linkage to underlying glycans, range of carriers, and complex spatial organization...
June 22, 2018: Xenotransplantation
Huan-Feng Zhu, Peng-Wei Yan, Li-Jun Wang, Ya-Tian Liu, Jing Wen, Qian Zhang, Yan-Xin Fan, Yan-Hong Luo
Huperzine A (HupA), derived from Huperzia Serrata, has exhibited a variety of biological actions, in particular neuroprotective effect. However, the protective activities of HupA on murine embryonic fibroblast NIH3T3 cells after X-rays radiation have not been fully elucidated. Herein, HupA treatment dramatically promoted cell viability, abated a G0/G1 peak accumulation, and ameliorated increase of cell apoptosis in NIH3T3 cells after X-rays radiation. Simultaneously, HupA notably enhanced activities of anti-oxidant enzymes, inhibited activity of lipid peroxide, and efficiently eliminated production of reactive oxygen species in NIH3T3 cells after X-rays radiation...
June 22, 2018: Journal of Cellular Biochemistry
Mahmood Rasool, Arif Malik, Ahmad Ashar Ghuman, Muhammad Abdul Basit Ashraf, Mahwish Arooj, Sulayman Waquar, Sara Zahid, Sumera Shaheen, Aamer Qazi, Muhammad Imran Naseer, Mazin A Zamzami, Ayat Al-Ghafari, Othman A Baothman, Mustafa Zeyadi, Nawal Helmi, Hani Choudhry, Mohammad Sarwar Jamal, Mohammed Hussein Al-Qahtani
Background: Colorectal cancer (CRC) is the third most common type of cancer and leading cause of death worldwide. Major risk factors involved in the development of CRC are increased dietary sources, genetics, and increasing age. Purpose of the study was to find the role of different variables in the progression of CRC. Methodology: 50 blood samples from CRC patients and 20 samples from control were collected. Serum was separated from the blood by centrifugation...
2018: Frontiers in Oncology
Juan Zhang, Defeng Li, Xiquan Yue, Meiling Zhang, Ping Liu, Genxi Li
Membrane-bound enzymes (MBEs), which make up a very high proportion of intracellular enzymes, catalyze a variety of activities that are currently analyzed by various techniques after purification. However, due to their amphipathic character, the purification of MBEs is difficult. Therefore, the most productive approach represents in situ analysis of MBEs in the cellular membrane. Methods: In this study, using membrane-bound α-glucosidase (α-Glu) as an example, we have developed a colorimetric in situ assay for MBEs based on the inhibitory effect of lipid bilayer on ion transport...
2018: Theranostics
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