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61.
62.
Changes in a phospholipid bilayer induced by the hydrolysis of a phospholipase A2 enzyme: a molecular dynamics simulation study 下载免费PDF全文
Phospholipase A2 (PLA2) enzymes are important in numerous physiological processes. Their function at lipid-water interfaces is also used as a biophysical model for protein-membrane interactions. These enzymes catalyze the hydrolysis of the sn-2 bonds of various phospholipids and the hydrolysis products are known to increase the activity of the enzymes. Here, we have applied molecular dynamics (MD) simulations to study the membrane properties in three compositionally different systems that relate to PLA2 enzyme action. One-nanosecond simulations were performed for a 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphatidylcholine (PLPC) bilayer and for two of its PLA2-hydrolyzed versions, i.e., bilayers consisting of lysophospholipids and of either free charged linoleate or free uncharged linoleic acid molecules. The results revealed loosening of the structure in the hydrolyzed bilayer due to increased mobility of the molecules in the direction normal to the bilayer. This loss of integrity due to the hydrolysis products is in accord with observations that not only the presence of hydrolysis products, but also a variety of other perturbations of the membrane may activate PLA2. Additionally, changes were observed in other structural parameters and in the electrostatic potential across the membrane-water interface. These changes are discussed in relation to the simulation methodology and the experimental observations of PLA2-hydrolyzed membranes. 相似文献
63.
Proteolytic enzymes of mast cell granules degrade low density lipoproteins and promote their granule-mediated uptake by macrophages in vitro 总被引:2,自引:0,他引:2
Secretory granules exocytosed from rat serosal mast cells bind low density lipoprotein (LDL), and on being phagocytosed by macrophages, carry the bound LDL into these cells (Kokkonen, J. O., and Kovanen, P. T. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 2287-2291). The binding of LDL to the granules is mediated through interactions between the apolipoprotein B (apoB) component of LDL and the heparin proteoglycan component of the granules. Here we report how degradation of apoB by the neutral proteases of the granules affects the granule-mediated uptake of LDL by cultured mouse macrophages. During incubation of LDL with proteolytically inactive granules, the rate of uptake of LDL by macrophages increased by 10-fold; whereas during incubation with proteolytically active granules, it increased by 50-fold, the increase in the rate of uptake during proteolysis correlating with the degree of apoB degradation. The 5-fold greater capacity of the proteolytically active granules to enhance the uptake of LDL resulted from their greater capacity to bind LDL, and consequently, to carry it into the macrophages. Electron microscopic analysis of LDL bound to the proteolytically active granules disclosed large spherical particles of fused LDL. The diameters of the granule-bound particles ranged up to 90 nm compared with an average diameter of 22 nm for both native LDL and the LDL bound to proteolytically inactive granules. The results show that granule proteases, by inducing fusion of granule-bound LDL, increase the amount of LDL bound per unit weight of granule heparin proteoglycan. Hence, the two components of mast cell granules, the proteases and the heparin proteoglycan, act in concert to promote the uptake of LDL by macrophages in vitro. 相似文献
64.
Pöllänen E Sipilä S Alen M Ronkainen PH Ankarberg-Lindgren C Puolakka J Suominen H Hämäläinen E Turpeinen U Konttinen YT Kovanen V 《Aging cell》2011,10(4):650-660
Aging is associated with gradual decline of skeletal muscle strength and mass often leading to diminished muscle quality. This phenomenon is known as sarcopenia and affects about 30% of the over 60-year-old population. Androgens act as anabolic agents regulating muscle mass and improving muscle performance. The role of female sex steroids as well as the ability of skeletal muscle tissue to locally produce sex steroids has been less extensively studied. We show that despite the extensive systemic deficit of sex steroid hormones in postmenopausal compared to premenopausal women, the hormone content of skeletal muscle does not follow the same trend. In contrast to the systemic levels, muscle tissue of post- and premenopausal women had similar concentrations of dehydroepiandrosterone and androstenedione, while the concentrations of estradiol and testosterone were significantly higher in muscle of the postmenopausal women. The presence of steroidogenetic enzymes in muscle tissue indicates that the elevated postmenopausal steroid levels in skeletal muscle are because of local steroidogenesis. The circulating sex steroids were associated with better muscle quality while the muscle concentrations reflected the amount of infiltrated fat within muscle tissue. We conclude that systemically delivered and peripherally produced sex steroids have distinct roles in the regulation of neuromuscular characteristics during aging. 相似文献
65.
66.
Bogdan Nowicki Mikael Rhen Vuokko Väisänen-Rhen Auli Pere Timo K. Korhonen 《FEMS microbiology letters》1985,28(3):237-242
Abstract The rate of fimbrial phase variation in Escherichia coli strain 3040 was determined. The strain has type-1 and S fimbriae. The bacterial culture was fractionated into homogeneous subpopulations expressing either one of the fimbrial types only; the subpopulations were inoculated into broth and the fimbriation of individual cells was assayed by immunofluorescence as a function of time. The rate of the shift from S- or type-1-fimbriate cells to non-fimbriate ones was of the order of 10−2 per cell generation and more rapid than a direct shift from one fimbrial phase to another, although both types of phase variations were observed. 相似文献
67.
Rintahaka J Wiik D Kovanen PE Alenius H Matikainen S 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(3):1749-1757
68.
Fractionation of a bacterial cell population by adsorption to erythrocytes and yeast cells 总被引:1,自引:0,他引:1
Bogdan Nowicki Mikael Rhen Vuokko Väisänen-Rhen Auli Pere Timo K. Korhonen 《FEMS microbiology letters》1985,26(1):35-40
Abstract Fluorochrome-labeled antibodies specific for either S or type-1 fimbriae of Escherichia coli were used to show that in broth culture the two fimbrial types of strain 3040 mostly occurred on different cells. 12% of the cells were nonfimbriated. A fractionation procedure that involved adsorption of bacterial cells onto erythrocytes and yeast cells was developed to isolate homogeneous subpopulations (S-fimbriated, type-1-fimbriated, and non-fimbriated) of. E. coli. The level of contamination in each isolated subpopulation was 4% at the highest. The method is useful in obtaining homogeneous bacterial populations for adherence studies and for purification of specific fimbrial antigens. 相似文献
69.
Human whole saliva contains two peroxidases, salivary peroxidase (hSPO) and myeloperoxidase (hMPO), which are part of the innate host defence in oral cavity. Both hSPO as well as human milk lactoperoxidase (hLPO) are coded by the same gene, but to what extent the different producing glands, salivary and mammary glands, affect the final conformation of the enzymes is not known. In human saliva the major function of hSPO and hMPO is to catalyze the oxidation of thiocyanate (SCN(-)) in the presence of hydrogen peroxide (H(2)O(2)) resulting in end products of wide antimicrobial potential. In addition cytotoxic H(2)O(2) is degraded. Similar peroxidation reactions inactivate some mutagenic and carcinogenic compounds, which suggests another protective mechanism of peroxidases in human saliva. Although being target of an active antimicrobial research, the structure-function relationships of hSPO are poorly known. However, recently published method for recombinant hSPO production offers new tools for those investigations. 相似文献
70.
Mast cell chymase induces smooth muscle cell apoptosis by disrupting NF-kappaB-mediated survival signaling 总被引:7,自引:0,他引:7
Leskinen MJ Heikkilä HM Speer MY Hakala JK Laine M Kovanen PT Lindstedt KA 《Experimental cell research》2006,312(8):1289-1298
Chymase released from activated mast cells induces apoptosis of vascular smooth muscle cells (SMCs) in vitro by degrading the pericellular matrix component fibronectin, so causing disruption of focal adhesion complexes and Akt dephosphorylation, which are necessary for cell adhesion and survival. However, the molecular mechanisms of chymase-mediated apoptosis downstream of Akt have remained elusive. Here, we show by means of RT-PCR, Western blotting, EMSA, immunocytochemistry and confocal microscopy, that chymase induces SMC apoptosis by disrupting NF-kappaB-mediated survival signaling. Following chymase treatment, the translocation of active NF-kappaB/p65 to the nucleus was partly abolished and the amount of nuclear p65 was reduced. Pretreatment of SMCs with chymase also inhibited LPS- and IL-1beta-induced nuclear translocation of p65. The chymase-induced degradation of p65 was mediated by active caspases. Loss of NF-kappaB-mediated transactivation resulted in downregulation of bcl-2 mRNA and protein expression, leading to mitochondrial swelling and release of cytochrome c. The apoptotic process involved activation of both caspase 9 and caspase 8. The results reveal that, by disrupting the NF-kappaB-mediated survival-signaling pathway, activated chymase-secreting mast cells can mediate apoptosis of cultured arterial SMCs. Since activated mast cells colocalize with apoptotic SMCs in vulnerable areas of human atherosclerotic plaques, they may participate in the weakening and rupture of atherosclerotic plaques. 相似文献