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101.
Atypical surface behavior of ceramides with nonhydroxy and 2-hydroxy very long-chain (C28–C32) PUFAs
Daniel A. Peñalva Gerardo M. Oresti Fernando Dupuy Silvia S. Antollini Bruno Maggio Marta I. Aveldaño María L. Fanani 《生物化学与生物物理学报:生物膜》2014
Unique species of ceramide (Cer) with very-long-chain polyunsaturated fatty acid (VLCPUFA), mainly 28–32 carbon atoms, 4–5 double bonds, in nonhydroxy and 2-hydroxy forms (n-V Cer and h-V Cer, respectively), are generated in rat spermatozoa from the corresponding sphingomyelins during the acrosomal reaction. The aim of this study was to determine the properties of these sperm-distinctive ceramides in Langmuir monolayers. Individual Cer species were isolated by HPLC and subjected to analysis of surface pressure, surface potential, and Brewster angle microscopy (BAM) as a function of molecular packing. In comparison with known species of Cer, n-V Cer and h-V Cer species showed much larger mean molecular areas and increased molecular dipole moments in liquid expanded phases, which suggest bending and partial hydration of the double bonded portion of the VLCPUFA. The presence of the 2-hydoxyl group induced a closer molecular packing in h-V Cer than in their chain-matched n-V Cer. In addition, all these Cer species showed liquid-expanded to liquid-condensed transitions at room temperature. Existence of domain segregation was confirmed by BAM. Additionally, thermodynamic analysis suggests a phase transition close to the physiological temperature for VLCPUFA-Cers if organized as bulk dispersions. 相似文献
102.
Pulmonary surfactant is an essential lipid–protein complex to maintain an operative respiratory surface at the mammalian lungs. It reduces surface tension at the alveolar air–liquid interface to stabilise the lungs against physical forces operating along the compression–expansion breathing cycles. At the same time, surfactant integrates elements establishing a primary barrier against the entry of pathogens. Lack or deficiencies of the surfactant system are associated with respiratory pathologies, which treatment often includes supplementation with exogenous materials. The present review summarises current models on the molecular mechanisms of surfactant function, with particular emphasis in its biophysical properties to stabilise the lungs and the molecular alterations connecting impaired surfactant with diseased organs. It also provides a perspective on the current surfactant-based strategies to treat respiratory pathologies. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. 相似文献
103.
Namandjé N. Bumpus 《Journal of inorganic biochemistry》2010,104(4):485-691
The site(s) of interaction between human cytochrome P450 2B6 and NADPH-cytochrome P450 reductase (P450 reductase) have yet to be identified. To investigate this, the cross-linking agent 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) was used to covalently link P450 2B6-P450 reductase. Following digestion with trypsin, the cross-linked peptides were identified by reconstituting the peptides in 18O-water based on the principle that the cross-linked peptides would be expected to incorporate twice as many 18O atoms as the non-cross-linked peptides. Subsequent mass spectrometric analyses of the resulting peptides led to the identification of one cross-linked peptide candidate. De novo sequencing of the peptide indicated that it is a complex between residues in the C-helix of the P450 (based upon solved X-ray crystal structures of P450 2B4) and the connecting domain of the P450 reductase. To confirm this experimentally, the P450 2B6 peptide identified through the cross-linking studies was synthesized and peptide competition studies were performed. In the presence of the synthetic peptide, P450 catalytic activity was decreased by up to 60% when compared to competition studies performed using a nonsense peptide. Taken together, these studies indicate that residues in the C-helix of P450 2B6 play a major role in the interaction with the P450 reductase. 相似文献
104.
Borroto-Escuela DO Romero-Fernandez W Tarakanov AO Marcellino D Ciruela F Agnati LF Fuxe K 《Biochemical and biophysical research communications》2010,401(4):605-610
In view of the co-distribution of dopamine D2LR and 5-hydroxytryptamine 5-HT2A receptors (D2LR and 5-HT2AR, respectively) within inter alia regions of the dorsal and ventral striatum and their role as a target of antipsychotic drugs; in this study we assessed the potential existence of D2LR-5-HT2AR heteromers in living cells and the functional consequences of this interaction. Thus, by means of a proximity-based bioluminescence resonance energy transfer (BRET) approach we demonstrated that the D2LR and the 5-HT2AR form stable and specific heteromers when expressed in HEK293T mammalian cells. Furthermore, when the D2LR-5-HT2AR heteromeric signaling was analyzed we found that the 5-HT2AR-mediated phospholipase C (PLC) activation was synergistically enhanced by the concomitant activation of the D2LR as shown in a NFAT-luciferase reporter gene assay and a specific and significant rise of the intracellular calcium levels were observed when both receptors were simultaneously activated. Conversely, when the D2LR-mediated adenylyl cyclase (AC) inhibition was assayed we showed that costimulation of D2LR and 5-HT2AR within the heteromer led to inhibition of the D2LR functioning, thus suggesting the existence of a 5-HT2AR-mediated D2LR trans-inhibition phenomenon. Finally, a bioinformatics study reveals that the triplet amino acid homologies LLT (Leu-Leu-Thr) and AIS (Ala-Ile-Ser) in TM1 and TM3, respectively of the D2R-5-HT2AR may be involved in the receptor interface. Overall, the presence of the D2LR-5-HT2AR heteromer in discrete brain regions is postulated based on the existence of D2LR-5-HT2A receptor-receptor interactions in living cells and their codistribution inter alia in striatal regions. Possible novel therapeutic strategies for treatment of schizophrenia should be explored by targeting this heteromer. 相似文献
105.
Dagmar Zunner Hans-Christian Kornau 《Biochemical and biophysical research communications》2010,393(2):185-189
GABAB receptors mediate slow inhibitory effects of the neurotransmitter γ-aminobutyric acid (GABA) on synaptic transmission in the central nervous system. They function as heterodimeric G-protein-coupled receptors composed of the seven-transmembrane domain proteins GABAB1 and GABAB2, which are linked through a coiled-coil interaction. The ligand-binding subunit GABAB1 is at first retained in the endoplasmic reticulum and is transported to the cell surface only upon assembly with GABAB2. Here, we report that GABAB1, via the coiled-coil domain, can also bind to soluble proteins of unknown function, that are affected in 22q11 deletion/DiGeorge syndrome and are therefore referred to as DiGeorge critical region 6 (DGCR6). In transfected neurons the GABAB1-DGCR6 association resulted in a redistribution of both proteins into intracellular clusters. Furthermore, the C-terminus of GABAB2 interfered with the novel interaction, consistent with heterodimer formation overriding transient DGCR6-binding to GABAB1. Thus, sequential coiled-coil interactions may direct GABAB1 into functional receptors. 相似文献
106.
Rodent species abundance and diversity in Western Serengeti are evaluated and discussed in relation to different levels of conservation status [Unprotected Area (UA), Game Reserve (GR) and National Park (NP)] and broad site differences in human livelihood activities. A total of 2170 individuals, spread over 16 rodent species, were caught in a capture‐mark‐recapture study which covered both the dry and wet seasons. The more humid site (Tabora B) in the northern part of Serengeti had the highest diversity of rodents followed by the Mihale site at the western extension. The driest site at Robanda had the lowest overall species diversity. Diversity also varied between the three levels of conservation status whereby the UA had the least diversity while the NP, which enjoyed the highest level of conservation status, had the highest diversity of rodents. Unprotected Area and NP plots at Tabora B showed a rodent species similarity index of 40%; all the other paired plots scored over 50% similarity indices, suggesting that, within a site, species composition did not vary significantly between the three levels of conservation status. The Robanda site had the highest (56%) overall abundance of rodents; Mihale and Tabora B sites had about the same level of rodent abundance (20 and 24% respectively). For the Mihale site, Mastomys natalensis ranked first followed by Arvicanthis niloticus and Tatera robusta, each of which contained 40, 38 and 16%, respectively, of all individuals caught at the site. For the Robanda site, the figures were 66%A. niloticus, 22%M. natalensis and 9%T. robusta; while for the Tabora B site the scores were 37%M. natalensis, 18%T. robusta and 11%Lemniscomys barbarus. The differences in diversity, species composition and population abundance appear to result largely from physiognomic vegetation types, and habitat perturbations caused by livelihood activities in Western Serengeti. 相似文献
107.
Bile salt interactions with phospholipid monolayers of fat emulsions are known to regulate the actions of gastrointestinal lipolytic enzymes in order to control the uptake of dietary fat. Specifically, on the lipid/aqueous interface of fat emulsions, the anionic portions of amphipathic bile salts have been thought to interact with and activate the enzyme group-IB phospholipase A2 (PLA2) derived from the pancreas. To explore this regulatory process, we have determined the crystal structures of the complexes of pancreatic PLA2 with the naturally occurring bile salts: cholate, glycocholate, taurocholate, glycochenodeoxycholate, and taurochenodeoxycholate. The five PLA2-bile salt complexes each result in a partly occluded active site, and the resulting ligand binding displays specific hydrogen bonding interactions and extensive hydrophobic packing. The amphipathic bile salts are bound to PLA2 with their polar hydroxyl and sulfate/carboxy groups oriented away from the enzyme's hydrophobic core. The impaired catalytic and interface binding functions implied by these structures provide a basis for the previous numerous observations of a biphasic dependence of the rate of PLA2 catalyzed hydrolysis of zwitterionic glycerophospholipids in the presence of bile salts. The rising or activation phase is consistent with enhanced binding and activation of the bound PLA2 by the bile salt induced anionic charge in a zwitterionic interface. The falling or inhibitory phase can be explained by the formation of a catalytically inert stoichiometric complex between PLA2 and any bile salts in which it forms a stable complex. The model provides new insight into the regulatory role that specific PLA2-bile salt interactions are likely to play in fat metabolism. 相似文献
108.
The interface between any newly engineered tissue and pre-existing tissue is of great importance to tissue engineering; however,
this process has so far been largely ignored, with few reports regarding the mechanical strength of newly integrated connective
tissues surfaces. A new model system has been developed to generate a well-defined interface between two collagen lattices:
one pre-contracted by resident fibroblasts and the other a cell-free wrapping gel. This construct can be cultured for prolonged
periods (>2 weeks) and can also be fitted onto a mechanical testing system to measure the interface adhesive strength at the
end of the culture time. Interface adhesive strength shows a six-fold increase after 1 week in culture, compared with the
time-zero baseline. Observations of cell migration across the interface suggest that cell translocation in the three-dimensional
matrix might play an important role in the integration process. In this new controlled geometry, normal and shear stresses
at the interface can be analysed by finite element modelling and the areas at which debonding starts can be defined. The current
experimental design permits solid multiple (homogeneous or heterogeneous) interface formation in vitro with a well-defined
geometry and the possibility of measuring mechanical linkage. This design should enable many other factors affecting cell-driven
interface strengthening to be investigated.
This study was supported by the Fifth Framework Programme of the European Commission, “Biomechanical Interactions in Tissue
Engineering and Surgical Repair (BITES)”. 相似文献
109.
Thermodynamic benchmark study using Biacore technology 总被引:1,自引:0,他引:1
Navratilova I Papalia GA Rich RL Bedinger D Brophy S Condon B Deng T Emerick AW Guan HW Hayden T Heutmekers T Hoorelbeke B McCroskey MC Murphy MM Nakagawa T Parmeggiani F Qin X Rebe S Tomasevic N Tsang T Waddell MB Zhang FF Leavitt S Myszka DG 《Analytical biochemistry》2007,364(1):67-77
A total of 22 individuals participated in this benchmark study to characterize the thermodynamics of small-molecule inhibitor-enzyme interactions using Biacore instruments. Participants were provided with reagents (the enzyme carbonic anhydrase II, which was immobilized onto the sensor surface, and four sulfonamide-based inhibitors) and were instructed to collect response data from 6 to 36 degrees C. van't Hoff enthalpies and entropies were calculated from the temperature dependence of the binding constants. The equilibrium dissociation and thermodynamic constants determined from the Biacore analysis matched the values determined using isothermal titration calorimetry. These results demonstrate that immobilization of the enzyme onto the sensor surface did not alter the thermodynamics of these interactions. This benchmark study also provides insights into the opportunities and challenges in carrying out thermodynamic studies using optical biosensors. 相似文献
110.
Maaria Kleemola Minna Toivonen Juha Mykkänen Kirsi Huoponen 《生物化学与生物物理学报:生物膜》2007,1768(10):2345-2354
y+LAT-1 and 4F2hc are the subunits of a transporter complex for cationic amino acids, located mainly in the basolateral plasma membrane of epithelial cells in the small intestine and renal tubules. Mutations in y+LAT-1 impair the transport function of this complex and cause a selective aminoaciduria, lysinuric protein intolerance (LPI, OMIM #222700), associated with severe, complex clinical symptoms. The subunits of an active transporter co-localize in the plasma membrane, but the exact process of dimerization is unclear since direct evidence for the assembly of this transporter in intact human cells has not been available. In this study, we used fluorescence resonance energy transfer (FRET) microscopy to investigate the interactions of y+LAT-1 and 4F2hc in HEK293 cells expressing y+LAT-1 and 4F2hc fused with ECFP or EYFP. FRET was quantified by measuring fluorescence intensity changes in the donor fluorophore (ECFP) after the photobleaching of the acceptor (EYFP). Increased donor fluorescence could be detected throughout the cell, from the endoplasmic reticulum and Golgi complex to the plasma membrane. Therefore, our data prove the interaction of y+LAT-1 and 4F2hc prior to the plasma membrane and thus provide evidence for 4F2hc functioning as a chaperone in assisting the transport of y+LAT-1 to the plasma membrane. 相似文献