DOCSLIB.ORG

Perspectives from Protein-Lipid

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Perspectives from Protein-Lipid Interaction of membrane-spanning proteins with peripheral and lipid-anchored membrane proteins: perspectives from protein ± lipid interactions (Review) D. Marsh{*, L. I. HorvaÂth{, M. J. Swamy}, translational diffusion in fluid bilayers, they can be distin- S. Mantripragada} and J. H. Kleinschmidt# guished from the latter in the spin label ESR spectrum. This is possible whenever the lipid rotational mobility differs substantially in the two environments (see figure 1). Then the {Max-Planck-Institut fuÈr biophysikalische Chemie, Abt. stoichiometry and specificity of lipid ± protein interaction can Spektroskopie, 37070 GoÈttingen, Germany be determined by using difference spectroscopyto quantitate the `free’ and protein-interacting lipid populations (Marsh {Institute of Biophysics, Biological Research Centre, 6701 1989). Szeged, Hungary Analysis of the lipid stoichiometry (Nb) and specificity (Kr) from the two-component ESR spectra uses the equation for }School of Chemistry, University of Hyderabad, Hyderabad equilibrium exchange association. The fraction, f, of spin- 5000046, India labelled lipid that is motionally restricted at one of the Nb sites at the intramembranous surface of the protein is given by }Skye Pharma, San Diego, CA 92121, USA (see Marsh 1985): #UniversitaÈt Konstanz, Fachbereich Biologie, 78457 f NbKr l nt Nb Kr 1 1 ˆ ‰ ‡ … ¡ †Š … † Konstanz, Germany where Kr is the average association constant of the spin- Summary labelled lipid relative to the host lipid and nt is the total lipid/ Studies of lipid ± protein interactions in double-reconstituted protein ratio. ESR titrations performed by varying the lipid/ systems involving both integral and peripheral or lipid-anchored protein ratio confirm that a fixed stoichiometry, Nb, is proteins are reviewed. Membranes of dimyristoyl phosphatidyl- maintained independent of nt (Brotherus et al. 1981), and glycerol containing either myelin proteolipid protein or cyto- yield values for both N and the mean relative association chrome c oxidase were studied. The partner peripheral proteins b bound to these membranes were myelin basic protein or constant Kr. In general, Kr&1 for a particular spin-labelled cytochrome c, respectively. In addition, the interactions between lipid (e.g. phosphatidylcholine) relative to its unlabelled the myelin proteolipid protein and avidin that was membrane- parent host lipid. This allows the determination of stoichio- anchored by binding to N-biotinyl phosphatidylethanolamine metries from measurements at a single lipid/protein ratio. were studied in dimyristoyl phosphatidylcholine membranes. It is expected that the lipid stoichiometry at the intramem- Steric exclusion plays a significant role when sizes of the peripheral protein and transmembrane domain of the integral branous perimeter is related directly to the transmembrane protein are comparable. Even so, the effects on avidin-linked structure and degree of oligomerization of the protein (Marsh lipids are different from those induced by myelin basic protein on 1997). Figure 2 compares ESR-determined values of Nb with freely diffusible lipids, both interacting with the myelin proteo- predictions for simple, regular helix packing arrangements. lipid protein. Both the former and the cytochrome c/cytochrome oxidase couple evidence a propagation of lipid perturbation out For a single monomeric helix (phospholamban mutant), and from the intramembrane protein interface that could be a basis for a monomeric 7-helix sandwich (rhodopsin), the predic- for formation of microdomains. tions work well. For proteolipid hexamers (PLP and 16kD), the stoichiometries per monomer are predictably reduced. Keywords: Lipid ± protein interactions, spin labels, electron spin For large, highly polytopic proteins such as cytochrome resonance, myelin proteins, cytochrome oxidase, avidin-biotin. oxidase (or acetylcholine receptor), with more complex and/ or less regular transmembrane arrangements, the simple models do not apply. Further discussion of this topic can be Introduction found in Marsh (1997) and Marsh and Horva th (1998). Electron spin resonance (ESR) with spin-labelled lipids at It is further expected that the selectivity patterns of lipid ± probe amounts has proved to be one of the most valuable protein interaction will reflect in detail the structure and spectroscopic methods for studying lipid ± protein interac- sequence of those sections of transmembrane protein tions in biological membranes (see e.g. Marsh 1985). This is segments that are located in the vicinity of the lipid because the dynamic sensitivity of spin-label ESR is headgroups. This expectation is borne out in practice by optimally matched to the timescale of the rotational motions the results of ESR studies. Figure 3 gives the values of Kr for of the lipid chains in biological membranes, which lies in the representative lipids interacting with a range of different ns range. Even if the exchange rate of the lipids at the membrane proteins. The lipid selectivity patterns differ for the intramembranous surface of an integral protein is as fast as different proteins. Whereas the highest selectivitiesare found for anionic lipids, they are not identical for lipids with the same formal charge, nor does a single lipid display the *To whom correspondence should be addressed. highest selectivity for all proteins. Cytochrome oxidase e-mail: [email protected] displays its highest selectivity for cardiolipin, a lipid unique Molecular Membrane Biology ISSN 0968-7688 print/ISSN 1464-5203 online # 2002 Taylor & Francis Ltd http://www.tandf.co.uk/journals DOI: 10.1080/09687680210162419 248 D. Marsh et al. Figure1. Schematic indication of the rotational mobility of the lipid andprotein components in membranes. The grey/ colourscale representsthe rotational correlation time of the different compo- nents.Motional restriction of the spin-labelled lipids in direct contact withthe transmembrane four-helix bundle results in a two-compo- nentESR spectrumfrom which the number of first-shell lipids is quantitated.The transmembrane topology of the myelin proteolipid Figure2. Dependence of the number of first-shell lipids, Nb per proteinis that determined in Weimbs and Stoffel (1992). The polar proteinmonomer, on the actual or predicted number of transmem- loopdeleted in theDM-20 isoform is also indicated. branehelices, na,forthe following integral proteins: M13, phage coat protein;PLB, L37A mutant of phospholamban; PLP, myelin proteolipidprotein; 16 kD, 16-kDa proteolipid from Nephrops; ADP, ADP-ATP carrier;Rho, rhodopsin; Ca, Ca-ATPase; NaK, Na,K- tomitochondria in eucaryotes, whereas rhodopsin displays ATPase;CR, cytochromereductase; AChR, acetylcholinereceptor; littleselectivity for any particular lipid species. This topic is CO, cytochromeoxidase. See Marsh (1997) for references. dealtwith further in Marsh (1995) and Marsh and Horva  th Predictionsfor helical sandwiches or regular polygonal arrange- (1998). ments(solid line) are given, where Da (=1 nm) and dch (=0.48 nm) Figures2 and3 showthat the database on lipid arethe diameters of an a-helixand a lipidchain, respectively. Dotted anddashed lines are corresponding predictions for protein dimers interactionswith single integral membrane protein species andhexamers, respectively. isreasonably extensive. As already implied, this area has beenreviewed several times, one of themost recent being in Marshand Horva th(1998), which also includes consideration ofthe penetration of soluble proteins into membranes. A forbiotin, this system serves as a modelfor covalent lipid considerablebody of work also exists on lipid interactions anchors.Also, because phospholipases must bind specifi- withsingle peripheral proteins. Some of thiswas reviewed in callyto thelipid headgroups, the avidin/ biotinlipid interaction Sankaramand Marsh (1993) and (Marsh (1995). Far fewer maybe used to model certain features of their mode of biophysicalstudies have been undertaken on the mutual interaction. interactionsof integral and peripheral proteins in defined Theway in which the lipid chains anchor the water-soluble reconstitutedsystems. This review is devoted specifically to avidinprotein to membranes was studied by using biotin- thisaspect of protein ± lipidinteractions, including protein- phosphatidylethanolamines(biotin-PE) that are spin-labelled linkedlipid chains. The latter are considered first, in the in their sn-2chain (Swamy and Marsh 1997). These absenceof a secondprotein, by using avidin bound to N- biotinylatedlipids were incorporated in membranes of biotinylphosphatidylethanola mineas amodelsystem. Then, phosphatidylcholine,an inert host lipid that alone does not themyelin basic protein/ myelinproteolipid and cytochrome bindavidin. Figure 4 givesthe lipid chain flexibility profile as a c/cytochromeoxidase couples are treated, followed finally by functionof position, n,ofspinlabelling, and the modification lipid-linkedavidin interacting with the proteolipid protein. ofthis profile by binding avidin. A systematicdecrease in the spectralouter hyperfine splitting, Amax,isfound as the spin- labelis stepped down the chain towards the centre of the Avidin/biotin-lipidmembrane anchoring membrane.This is a measureof the angular amplitude of Phosphatidylethanolaminesthatare N-derivatisedwith biotin motionalfreedom of the lipid chain segments. The char- canspecifically bind the protein avidin (see e.g. Swamy and acteristicflexibility gradient thus registered by the spin- Marsh2001). Because of the extremely high affinity of avidin labelledlipid
Load more

Recommended publications
  • A Unique Structure at the Carboxyl Terminus of the Largest Subunit of Eukaryotic RNA Polymerase II (Transcription/Gene Expression/Protein Phosphorylation) JEFFRY L
    Proc. Natl. Acad. Sci. USA Vol. 82, pp. 7934-7938, December 1985 Biochemistry A unique structure at the carboxyl terminus of the largest subunit of eukaryotic RNA polymerase II (transcription/gene expression/protein phosphorylation) JEFFRY L. CORDEN*, DEBORAH L. CADENAt, JOSEPH M. AHEARN, JR.*, AND MICHAEL E. DAHMUSt *Howard Hughes Medical Institute Laboratory, Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and tDepartment of Biochemistry and Biophysics, University of California, Davis, CA 95616 Communicated by Daniel Nathans, August 2, 1985 ABSTRACT Purified eukaryotic nuclear RNA polymerase alous mobility in NaDodSO4 gels due to postsynthetic mod- II consists of three subspecies that differ in the apparent ification cannot be ruled out. The three forms of the largest molecular masses of their largest subunit, designated Ho, Ha, subunit Ho (240 kDa), Iha (210-220 kDa), and lIb (170-180 and HIb for polymerase species HO, HA, and BIB, respectively. kDa) also differ in their ability to be phosphorylated both in Subunits Ho, Ha, and IHb are the products of a single gene. We vitro and in vivo (14). Subunit lIc (140 kDa) is structurally present here the amino acid composition of calf thymus different from IHo, Iha, and IIb (2, 33) and is present in all subunits Ha and lIb and the C-terminal amino acid sequence three forms of RNA polymerase II in equimolar stoichiom- of subunit Ha (Ho) inferred from the nucleotide sequence of etry with the largest subunit. part of the mouse gene encoding this RNA polymerase subunit. A monoclonal antibody prepared against calfthymus RNA The calculated amino acid composition ofthe peptide unique to polymerase II has been shown to recognize a determinant on subunit Ha indicates that subunit Ha contains a domain rich in subunit Iha (IIo) but not on IIb (15).
    [Show full text]
  • Immunoglobulin G Is a Platelet Alpha Granule-Secreted Protein
    Immunoglobulin G is a platelet alpha granule-secreted protein. J N George, … , L K Knieriem, D F Bainton J Clin Invest. 1985;76(5):2020-2025. https://doi.org/10.1172/JCI112203. Research Article It has been known for 27 yr that blood platelets contain IgG, yet its subcellular location and significance have never been clearly determined. In these studies, the location of IgG within human platelets was investigated by immunocytochemical techniques and by the response of platelet IgG to agents that cause platelet secretion. Using frozen thin-sections of platelets and an immunogold probe, IgG was located within the alpha-granules. Thrombin stimulation caused parallel secretion of platelet IgG and two known alpha-granule proteins, platelet factor 4 and beta-thromboglobulin, beginning at 0.02 U/ml and reaching 100% at 0.5 U/ml. Thrombin-induced secretion of all three proteins was inhibited by prostaglandin E1 and dibutyryl-cyclic AMP. Calcium ionophore A23187 also caused parallel secretion of all three proteins, whereas ADP caused virtually no secretion of any of the three. From these data and a review of the literature, we hypothesize that plasma IgG is taken up by megakaryocytes and delivered to the alpha-granules, where it is stored for later secretion by mature platelets. Find the latest version: https://jci.me/112203/pdf Rapid Publication Immunoglobulin G Is a Platelet Alpha Granule-secreted Protein James N. George, Sherry Saucerman, Shirley P. Levine, and Linda K. Knieriem Division ofHematology, Department ofMedicine, University of Texas Health Science Center, and Audie L. Murphy Veterans Hospital, San Antonio, Texas 78284 Dorothy F.
    [Show full text]
  • Conservation of Topology, but Not Conformation, of the Proteolipid Proteins of the Myelin Sheath
    The Journal of Neuroscience, January 1, 1997, 17(1):181–189 Conservation of Topology, But Not Conformation, of the Proteolipid Proteins of the Myelin Sheath Alexander Gow,1 Alexander Gragerov,1 Anthony Gard,2 David R. Colman,1 and Robert A. Lazzarini1 1Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029-6574, and 2Department of Structural and Cell Biology, University of South Alabama College of Medicine, Mobile, Alabama 36688 The proteolipid protein gene products DM-20 and PLP are during de novo synthesis. Surprisingly, the conformation (as adhesive intrinsic membrane proteins that make up $50% of opposed to topology) of DM-20 and PLP may differ, which has the protein in myelin and serve to stabilize compact myelin been inferred from the divergent effects that many missense sheaths at the extracellular surfaces of apposed membrane mutations have on the intracellular trafficking of these two lamellae. To identify which domains of DM-20 and PLP are isoforms. The 35 amino acid cytoplasmic peptide in PLP, which positioned topologically in the extracellular space to participate distinguishes this protein from DM-20, imparts a sensitivity to in adhesion, we engineered N-glycosylation consensus sites mutations in extracellular domains. This peptide may normally into the hydrophilic segments and determined the extent of function during myelinogenesis to detect conformational glycosylation. In addition, we assessed the presence of two changes originating across the bilayer from extracellular PLP translocation stop-transfer signals and, finally, mapped the interactions in trans and trigger intracellular events such as extracellular and cytoplasmic dispositions of four antibody membrane compaction in the cytoplasmic compartment.
    [Show full text]
  • In Silico Perspectives on the Prediction of the PLP’S Epitopes Involved in Multiple Sclerosis
    Iranian J Biotech. 2017 January;15(1):e1356 DOI: 10.15171/ijb.1356 Research Article In Silico Perspectives on the Prediction of the PLP’s Epitopes involved in Multiple Sclerosis Zahra Zamanzadeh1, Mitra Ataei1, Seyed Massood Nabavi2, Ghasem Ahangari1, Mehdi Sadeghi1, Mohammad Hosein Sanati1,* 1 Department of medical biotechnology. Institute of Medical Genetic, National Institute of Genetics Engineering and Biotechnology (NIGEB), Tehran, 14965/161 Iran 2 Department of Neurology, Faculty of Public Health, Shahed University, Tehran, 18155/159, Iran *Corresponding author: Department of Medical Genetic, National Institute of Genetic Engineering and Biotechnology (NIGEB), Shahrak-e- Pajoohesh, 15th Km, Tehran-Karaj Highway, Tehran, 14965-161, Iran. Tel.: +98 21 44780365; Fax: +98 21 44780395; E-mail: [email protected] Received: 15 Sep. 2015 Revised: 29 May 2016 Accepted: 13 March 2017 Published online: 31 May 2017 Background: Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade. Objectives: The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein (PLP) in multiple sclerosis. Materials and Methods: As there wasn’t any tertiary structure of PLP available in the Protein Data Bank (PDB) and in order to characterize the structural properties of the protein, we modeled this protein using prediction servers. Meta prediction method, as a new perspective in silico, was performed to fi nd PLPs epitopes.
    [Show full text]
  • The Principles and Applications of Avidin-Based Nanoparticles in Drug Delivery and Diagnosis
    Journal of Controlled Release 245 (2017) 27–40 Contents lists available at ScienceDirect Journal of Controlled Release journal homepage: www.elsevier.com/locate/jconrel Review article The principles and applications of avidin-based nanoparticles in drug delivery and diagnosis Akshay Jain, Kun Cheng ⁎ Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, MO 64108, United States article info abstract Article history: Avidin-biotin interaction is one of the strongest non-covalent interactions in the nature. Avidin and its analogues Received 7 October 2016 have therefore been extensively utilized as probes and affinity matrices for a wide variety of applications in bio- Accepted 7 November 2016 chemical assays, diagnosis, affinity purification, and drug delivery. Recently, there has been a growing interest in Available online 16 November 2016 exploring this non-covalent interaction in nanoscale drug delivery systems for pharmaceutical agents, including small molecules, proteins, vaccines, monoclonal antibodies, and nucleic acids. Particularly, the ease of fabrication Keywords: Nanotechnology without losing the chemical and biological properties of the coupled moieties makes the avidin-biotin system a Avidin versatile platform for nanotechnology. In addition, avidin-based nanoparticles have been investigated as Neutravidin diagnostic systems for various tumors and surface antigens. In this review, we will highlight the various Streptavidin fabrication principles and biomedical applications of avidin-based nanoparticles in drug delivery and diagnosis. Non-covalent interaction The structures and biochemical properties of avidin, biotin and their respective analogues will also be discussed. Drug delivery © 2016 Elsevier B.V. All rights reserved. Imaging Diagnosis Contents 1. Introduction............................................................... 27 2. Biochemicalinsightsofavidin,biotinandanalogues............................................
    [Show full text]
  • How Does Protein Zero Assemble Compact Myelin?
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 13 May 2020 doi:10.20944/preprints202005.0222.v1 Peer-reviewed version available at Cells 2020, 9, 1832; doi:10.3390/cells9081832 Perspective How Does Protein Zero Assemble Compact Myelin? Arne Raasakka 1,* and Petri Kursula 1,2 1 Department of Biomedicine, University of Bergen, Jonas Lies vei 91, NO-5009 Bergen, Norway 2 Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Aapistie 7A, FI-90220 Oulu, Finland; [email protected] * Correspondence: [email protected] Abstract: Myelin protein zero (P0), a type I transmembrane protein, is the most abundant protein in peripheral nervous system (PNS) myelin – the lipid-rich, periodic structure that concentrically encloses long axonal segments. Schwann cells, the myelinating glia of the PNS, express P0 throughout their development until the formation of mature myelin. In the intramyelinic compartment, the immunoglobulin-like domain of P0 bridges apposing membranes together via homophilic adhesion, forming a dense, macroscopic ultrastructure known as the intraperiod line. The C-terminal tail of P0 adheres apposing membranes together in the narrow cytoplasmic compartment of compact myelin, much like myelin basic protein (MBP). In mouse models, the absence of P0, unlike that of MBP or P2, severely disturbs the formation of myelin. Therefore, P0 is the executive molecule of PNS myelin maturation. How and when is P0 trafficked and modified to enable myelin compaction, and how disease mutations that give rise to incurable peripheral neuropathies alter the function of P0, are currently open questions. The potential mechanisms of P0 function in myelination are discussed, providing a foundation for the understanding of mature myelin development and how it derails in peripheral neuropathies.
    [Show full text]
  • ELISA Kit for Hemopexin (HPX)
    SEB986Ra 96 Tests Enzyme-linked Immunosorbent Assay Kit For Hemopexin (HPX) Organism Species: Rattus norvegicus (Rat) Instruction manual FOR IN VITRO AND RESEARCH USE ONLY NOT FOR USE IN CLINICAL DIAGNOSTIC PROCEDURES 11th Edition (Revised in July, 2013) [ INTENDED USE ] The kit is a sandwich enzyme immunoassay for in vitro quantitative measurement of hemopexin in rat serum, plasma and other biological fluids. [ REAGENTS AND MATERIALS PROVIDED ] Reagents Quantity Reagents Quantity Pre-coated, ready to use 96-well strip plate 1 Plate sealer for 96 wells 4 Standard 2 Standard Diluent 1×20mL Detection Reagent A 1×120μL Assay Diluent A 1×12mL Detection Reagent B 1×120μL Assay Diluent B 1×12mL TMB Substrate 1×9mL Stop Solution 1×6mL Wash Buffer (30 × concentrate) 1×20mL Instruction manual 1 [ MATERIALS REQUIRED BUT NOT SUPPLIED ] 1. Microplate reader with 450 ± 10nm filter. 2. Precision single or multi-channel pipettes and disposable tips. 3. Eppendorf Tubes for diluting samples. 4. Deionized or distilled water. 5. Absorbent paper for blotting the microtiter plate. 6. Container for Wash Solution [ STORAGE OF THE KITS ] 1. For unopened kit: All the reagents should be kept according to the labels on vials. The Standard, Detection Reagent A, Detection Reagent B and the 96-well strip plate should be stored at -20oC upon receipt while the others should be at 4 oC. 2. For opened kit: When the kit is opened, the remaining reagents still need to be stored according to the above storage condition. Besides, please return the unused wells to the foil pouch containing the desiccant pack, and reseal along entire edge of zip-seal.
    [Show full text]
  • Structural Insights Into Membrane Fusion Mediated by Convergent Small Fusogens
    cells Review Structural Insights into Membrane Fusion Mediated by Convergent Small Fusogens Yiming Yang * and Nandini Nagarajan Margam Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada; [email protected] * Correspondence: [email protected] Abstract: From lifeless viral particles to complex multicellular organisms, membrane fusion is inarguably the important fundamental biological phenomena. Sitting at the heart of membrane fusion are protein mediators known as fusogens. Despite the extensive functional and structural characterization of these proteins in recent years, scientists are still grappling with the fundamental mechanisms underlying membrane fusion. From an evolutionary perspective, fusogens follow divergent evolutionary principles in that they are functionally independent and do not share any sequence identity; however, they possess structural similarity, raising the possibility that membrane fusion is mediated by essential motifs ubiquitous to all. In this review, we particularly emphasize structural characteristics of small-molecular-weight fusogens in the hope of uncovering the most fundamental aspects mediating membrane–membrane interactions. By identifying and elucidating fusion-dependent functional domains, this review paves the way for future research exploring novel fusogens in health and disease. Keywords: fusogen; SNARE; FAST; atlastin; spanin; myomaker; myomerger; membrane fusion 1. Introduction Citation: Yang, Y.; Margam, N.N. Structural Insights into Membrane Membrane fusion
    [Show full text]
  • Lysis of Red Blood Cells and Alveolar Epithelial Toxicity by Therapeutic Pulmonary Surfactants
    0031-3998/95/3701-0026$03.0010 PEDIATRIC RESEARCH Vol. 37, No. 1, 1995 Copyright 0 1994 International Pediatric Research Foundation, Inc. Printed in U.S.A. Lysis of Red Blood Cells and Alveolar Epithelial Toxicity by Therapeutic Pulmonary Surfactants RICHARD D. FINDLAY, H. WILLIAM TAEUSCH, REMEDIOS DAVID-CU, AND FRANS J. WALTHER Division of Neonatology, Department of Pediatrics, Martin Luther King, Jr./Drew University Medical Center, UCLA School of Medicine, Los Angeles, Calijornia 90059 The risk of pulmonary hemorrhage is increased in extremely rats were treated with Survanta, Exosurf, the Exosurf compo- low birth weight infants treated with surfactant. The pathogenesis nents tyloxapol and hexadecanol, melittin, or culture medium of this increased risk is far from clear. We tested whether alone. After 24 h of incubation, lactate dehydrogenase release exposure of cell membranes to surfactant may lead to increased into the media was measured as a percent of total lactate dehy- membrane permeability, hypothesizing that this process may drogenase activity to indicate cytotoxicity. Lactate dehydroge- contribute to the occurrence of alveolar hemorrhage after surfac- nase release was <lo% for control experiments but increased tant treatment. Aliquots of washed packed red blood cells (used sharply with Exosurf and its components tyloxapol and hexade- as membrane model) were suspended in 0.9% NaCl with various canol. These results indicate that surfactant may be associated concentrations of Survanta or Exosurf for either 2 or 24 h at with in vitro cytotoxicity and that this property differs for dif- 37°C. Cytolysis was measured by spectrophotometric determi- ferent surfactants and different dosages. (Pediatr Res 37: 26-30, nation of free Hb after centrifugation.
    [Show full text]
  • The Crosstalk: Exosomes and Lipid Metabolism
    Wang et al. Cell Communication and Signaling (2020) 18:119 https://doi.org/10.1186/s12964-020-00581-2 REVIEW Open Access The crosstalk: exosomes and lipid metabolism Wei Wang1,2†, Neng Zhu3†, Tao Yan1,2†, Ya-Ning Shi1,2, Jing Chen4, Chan-Juan Zhang1,2, Xue-Jiao Xie5, Duan-Fang Liao1,2* and Li Qin1,2* Abstract Exosomes have been considered as novel and potent vehicles of intercellular communication, instead of “cell dust”. Exosomes are consistent with anucleate cells, and organelles with lipid bilayer consisting of the proteins and abundant lipid, enhancing their “rigidity” and “flexibility”. Neighboring cells or distant cells are capable of exchanging genetic or metabolic information via exosomes binding to recipient cell and releasing bioactive molecules, such as lipids, proteins, and nucleic acids. Of note, exosomes exert the remarkable effects on lipid metabolism, including the synthesis, transportation and degradation of the lipid. The disorder of lipid metabolism mediated by exosomes leads to the occurrence and progression of diseases, such as atherosclerosis, cancer, non- alcoholic fatty liver disease (NAFLD), obesity and Alzheimer’s diseases and so on. More importantly, lipid metabolism can also affect the production and secretion of exosomes, as well as interactions with the recipient cells. Therefore, exosomes may be applied as effective targets for diagnosis and treatment of diseases. Keywords: Exosome, Lipid metabolism, Atherosclerosis, Cancer Background the membrane [8]. Similar to the cell membrane, the lipid Exosomes display cup-like shape of 30 ~ 100 nm in diam- bilayer protects exosome contents from various stimuli in eter, and are secreted by multi-type cells, such as nerve thecirculatingfluid.Therefore,somecontentsinexo- cells [1], natural killer cells [2, 3], cancer cells [4, 5]and somes are usually transported remotely in circulating body adipocytes [6].
    [Show full text]
  • Inhibitory Effects of Activin on the Growth and Morphogenesis of Primary and Transformed Mammary Epithelial Cells'
    ICANCERRESEARCH56. I 155-I 163. March I. 19961 Inhibitory Effects of Activin on the Growth and Morphogenesis of Primary and Transformed Mammary Epithelial Cells' Qiu Yan Liu, Birunthi Niranjan, Peter Gomes, Jennifer J. Gomm, Derek Davies, R. Charles Coombes, and Lakjaya Buluwela2 Departments of Medical Oncology (Q. Y. L, P. G.. J. J. G., R. C. C., L B.J and Biochemistry (Q. Y. L. L B.J. Charing Cross and Westminster Medical School, Fuiham Palace Road. London W6 8RF; Division of Cell Biology and Experimental Pathology. Institute of Cancer Research, 15 Cotswald Rood, Sutton. Surrey SM2 SNG (B. NJ; and FACS Analysis Laboratory. imperial Cancer Research Fund, Lincoln ‘sInnFields. London WC2A 3PX (D. DI, United Kingdom ABSTRACT logical activities of activin. Indeed, two types of activin receptors have aLready been identified in the mouse (28) and several forms in Activin Is a member of the transforming growth factor fi superfamily, Xenopus (29, 30). The sequences of the Act-RI! (3 1), the TGF-@ type which is known to have activities Involved In regulating differentiation II receptor (32), the TGF-f3 type I receptor (33), and various activin and development. By using reverse transcrlption.PCR analysis on immu noafflnity.purlfied human breast cells, we have found that activin IJa and receptor-like genes (34) have been described. The comparison of these activin type II receptor are expressed by myoepithelial cells, whereas no sequences shows that they belong to a newly defined family of expression was detected In other breast cell types. In examining 15 breast membrane-bound, ligand-activated serine-threonine kinases (35).
    [Show full text]
  • Testicular Expression of Inhibin and Activin Subunits and Follistatin in the Rat and Human Fetus and Neonate and During Postnatal Development in the Rat*
    0013-7227/97/$03.00/0 Vol. 138, No. 5 Endocrinology Printed in U.S.A. Copyright © 1997 by The Endocrine Society Testicular Expression of Inhibin and Activin Subunits and Follistatin in the Rat and Human Fetus and Neonate and During Postnatal Development in the Rat* GREGOR MAJDIC, ALLAN S. MCNEILLY, RICHARD M. SHARPE, LEE R. EVANS, NIGEL P. GROOME, AND PHILIPPA T. K. SAUNDERS Medical Research Council Reproductive Biology Unit (G.M., A.S.M., R.M.S., P.T.K.S.), Edinburgh, EH3 9EW, United Kingdom; and the School of Biological and Molecular Sciences (L.R.E., N.P.G.), Oxford Brookes University, Headington, Oxford, OX3 0BP, United Kingdom ABSTRACT than immunostaining for the a-subunit. The pattern of bB-immuno- Inhibins, activins, and follistatins are all believed to play roles in staining in postnatal samples paralleled that of the a-subunit. Im- the regulation of FSH secretion by the pituitary and in the paracrine munostaining using antibodies against the bA-subunit did not pro- regulation of testis function. Previous studies have resulted in con- duce any significant reaction product in any sample. Follistatin was flicting data on the pattern of expression of the inhibin/activin sub- undetectable in the fetal rat testis but appeared in the Leydig cells units, and little information on expression of follistatin during fetal/ immediately after birth and its expression remained intense through- neonatal life. We have made use of new, highly specific monoclonal out postnatal development and in adult testis. No evidence was ob- antibodies and fixed tissue sections from fetal, neonatal, and adult tained for expression of either the inhibin/activin subunits or follista- rats, and limited amounts of fetal and neonatal human testis, to tin in the germ cells, peritubular myoid cells, or other interstitial cells undertake a detailed immunocytochemical study of the pattern of in any of the sections examined.
    [Show full text]