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991.
The intraerythrocytic Plasmodium falciparum parasite converts most of host hemoglobin heme into a nontoxic heme crystal. Erythrocyte zinc protoporphyrin IX, normally present at 0.5 microM, which is a ratio of 1:40,000 hemes, can elevate 10-fold in some of the anemias associated with malaria disease protection. This work examines a binding mechanism for zinc protoporphyrin IX inhibition of heme crystallization similar to the antimalarial quinolines. Zinc protoporphyrin IX neither forms crystals alone nor extends on preformed heme crystals. Inhibition of both seed heme crystal formation and crystal extension occurs with an inhibitory concentration (IC)50 of 5 microM. Field emission in-lens scanning electron microscopy depicts the transition and inhibition of heme monomer aggregates to heme crystals with and without seeding of preformed hemozoin templates. In vitro zinc protoporphyrin IX, like the quinolines, binds to heme crystals in a saturable, specific, pH, and time-dependent manner. The ratio at saturation is approximately 1 zinc protoporphyrin IX per 250 hemes of the crystal. Unlike the quinolines, zinc protoporphyrin IX binds measurably in the absence of heme. Isolated ring and trophozoite stage parasites have an elevated zinc protoporphyrin IX to heme ratio 6 to 10 times that in the erythrocyte cytosol, which also corresponds to elevated ratios found in heme crystals purified from Plasmodium parasites. This work implicates protection from malaria by a mechanism where elevated zinc protoporphyrin IX in anemic erythrocytes binds to heme crystals to inhibit further crystallization. In endemic malaria areas, severe iron deficiency anemia should be treated with antimalarials along with iron replenishment. 相似文献
992.
RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain 总被引:21,自引:0,他引:21
Deane R Du Yan S Submamaryan RK LaRue B Jovanovic S Hogg E Welch D Manness L Lin C Yu J Zhu H Ghiso J Frangione B Stern A Schmidt AM Armstrong DL Arnold B Liliensiek B Nawroth P Hofman F Kindy M Stern D Zlokovic B 《Nature medicine》2003,9(7):907-913
Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta interaction with receptor for advanced glycation end products (RAGE)-bearing cells in the vessel wall results in transport of Abeta across the blood-brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1 (ET-1), the latter mediating Abeta-induced vasoconstriction. Inhibition of RAGE-ligand interaction suppresses accumulation of Abeta in brain parenchyma in a mouse transgenic model. These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Abeta-vascular interactions, including development of cerebral amyloidosis. 相似文献
993.
We describe here a new approach to construct a multilayer enzyme/polyelectrolyte film on a structured transparent indium-tin oxide (ITO) covered glass electrode surface as micropattern, on which two different types of enzyme distributed laterally on one common substrate without interference. The multilayer film was prepared by alternate electric field directed layer-by-layer assembly deposition and alternate deposition of different redox enzymes and polyelectrolyte poly(diallyldimethylammonium chloride) (PDDA) onto the site-selective ITO glass electrode surface. The cyclic voltammogram, obtained from the ITO glass electrode modified with the glucose oxidase (GO(X))/PDDA and catalase (CA(T))/PDDA multilayers, revealed that the bioelectrocatalytic response is directly correlated to the number of deposition bilayers. From the analysis of cyclic voltammetric characterization, the coverage of catalytically active enzymes per enzyme/PDDA bilayer during the multilayer formation was homogeneous, which demonstrates that the multilayer is constructed in a spatially ordered manner. Also, from the atomic force microscopy and Brewster angle microscopy measurements, more information of the multilayer constructed by different methods on the modified electrode surface is obtained and compared. This fabrication technique is simple and would be applicable to the construction of a thickness- and area-controlled biopattern composed of multi-enzymes as well as multiple biomaterials. 相似文献
994.
995.
Adrenomedullin is a potent vasodilator peptide originally isolated from a pheochromocytoma. Recently, a novel adrenomedullin receptor has been identified as a complex of calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 2 (RAMP2). To explore the pathophysiological roles of adrenomedullin and its receptor component RAMP2 in ischemic cardiovascular diseases, we studied the changes of adrenomedullin and RAMP2 mRNA in myocardium and aorta in rats with isoproterenol (ISO)-induced myocardial impairment. In ISO-treated rats, heart became enlarged markedly, the ratio of heart to body weight was increased by 54% (P<0.01), and myocardial malondialdehyde content and plasma lactate dehydrogenase activity was elevated by 43% (P<0.01) and 138% (P<0.01), respectively. Immunoreactive adrenomedullin (ADM) in plasma, myocardium and aorta was augmented by 116.7% (P<0.01), 50.8% (P<0.01) and 12.5% (P>0.05), respectively. ADM mRNA in myocardium and aorta was increased by 96.8% (P<0.01) and 38.5% (P<0.01), respectively. RAMP2 mRNA in myocardium and aorta was increased by 19.6% (P<0.05) and 15.8% (P<0.01), respectively. These results suggest that the increase of ADM level and the up-regulation of ADM and RAMP2 gene in myocardium and aorta may be significant in the pathogenesis of ischemic myocardiopathy. 相似文献
996.
Transmodulation between phospholipase D and c-Src enhances cell proliferation 总被引:4,自引:0,他引:4 下载免费PDF全文
Ahn BH Kim SY Kim EH Choi KS Kwon TK Lee YH Chang JS Kim MS Jo YH Min DS 《Molecular and cellular biology》2003,23(9):3103-3115
Phospholipase D (PLD) has been implicated in the signal transduction pathways initiated by several mitogenic protein tyrosine kinases. We demonstrate for the first time that most notably PLD2 and to a lesser extent the PLD1 isoform are tyrosine phosphorylated by c-Src tyrosine kinase via direct association. Moreover, epidermal growth factor induced tyrosine phosphorylation of PLD2 and its interaction with c-Src in A431 cells. Interaction between these proteins is via the pleckstrin homology domain of PLD2 and the catalytic domain of c-Src. Coexpression of PLD1 or PLD2 with c-Src synergistically enhances cellular proliferation compared with expression of either molecule. While PLD activity as a lipid-hydrolyzing enzyme is not affected by c-Src, wild-type PLDs but not catalytically inactive PLD mutants significantly increase c-Src kinase activity, up-regulating c-Src-mediated paxillin phosphorylation and extracellular signal-regulated kinase activity. These results demonstrate the critical role of PLD catalytic activity in the stimulation of Src signaling. In conclusion, we provide the first evidence that c-Src acts as a kinase of PLD and PLD acts as an activator of c-Src. This transmodulation between c-Src and PLD may contribute to the promotion of cellular proliferation via amplification of mitogenic signaling pathways. 相似文献
997.
This report assessed the effect of overexpressing Cu,Zn superoxide dismutase (SOD) and/or catalase on the interaction of mononuclear cells (MNCs) and endothelial cells (ECs). ECs were obtained from the aorta of wild-type mice and transgenic mice overexpressing Cu,ZnSOD and/or catalase. MNCs were obtained from wild-type mice. Treatment of wild-type ECs with CuSO4-oxidized low-density lipoprotein (oxLDL) significantly elevated the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and increased the adherence of MNCs. Overexpression of Cu,ZnSOD and/or catalase in ECs attenuated the adherence of MNCs and the expression of cell adhesion molecules induced by oxLDL. For example, ECs overexpressing Cu,ZnSOD and/or catalase showed significantly less expression of VCAM-1 and ICAM-1 and less number of adherent MNCs than wild-type ECs. Moreover, ECs overexpressing Cu,ZnSOD and catalase in combination showed significantly less expression of VCAM-1 and ICAM-1 and less number of adherent MNCs than those overexpressing either Cu,ZnSOD or catalase alone. These results suggest that combinational overexpression of Cu,ZnSOD and catalase can reduce the expression of cell adhesion molecules and inhibit the adherence of leukocyte to ECs more efficiently than overexpression of Cu,ZnSOD or catalase alone. 相似文献
998.
Renal aquaporins and sodium transporters with special focus on urinary tract obstruction 总被引:3,自引:0,他引:3
Frøkiaer J Li C Shi Y Jensen A Praetorius H Hansen H Topcu O Sardeli C Wang W Kwon TH Nielsen S 《APMIS. Supplementum》2003,(109):71-79
The discovery of aquaporin-1 (AQP1) by Agre and colleagues explained the long-standing biophysical question of how water specifically crosses biological membranes. These studies led to the discovery and identification of a whole new family of membrane proteins, the aquaporins. At present, at least seven aquaporins are expressed at distinct sites in the kidney and 4 members of this family (AQP1-4) have been demonstrated to play pivotal roles in the physiology and pathophysiology for renal regulation of body water balance. Osmotic equilibration via renal aquaporins is maintained by active transport of NaCl. The major sodium transporters and channels in the individual renal tubule segments have been identified and the regulation of these transporters and channels are fundamental for renal sodium reabsorption and for establishing the driving force. In this mini-review the role of renal aquaporins and sodium transporters and channels is briefly described and their key role for the impaired urinary concentrating capacity in response to urinary tract obstruction is reviewed. Thus this review updates previous detailed reviews (1-5). 相似文献
999.
Structural insights on Smad function in TGFbeta signaling 总被引:1,自引:0,他引:1
Shi Y 《BioEssays : news and reviews in molecular, cellular and developmental biology》2001,23(3):223-232
TGFbeta signaling plays a central role in regulating a broad range of cellular responses in a variety of organisms. TGFbeta signaling from the cell membrane to the nucleus is mediated by the Smad family of proteins. During the past five years of intense investigation, key events in TGFbeta signaling have been documented at the molecular and cellular level. Recent structural studies have improved our understanding of how specificity is generated in the TGFbeta signaling pathways. Despite this progress, significant questions remain regarding the precise mechanisms of signaling and point to the urgent need for well-controlled biochemical studies. Rather than giving a comprehensive review on Smad-mediated TGFbeta signaling, this review focuses on functional insights provided by recent structural studies and discusses several existing controversies. 相似文献
1000.
Shi XW Fitzsimmons CJ Genêt C Prather R Whitworth K Green JA Tuggle CK 《Animal genetics》2001,32(4):205-209
A comparative study of human chromosome 17 (HSA17) and pig chromosome 12 (SSC12) was conducted using both somatic cell hybrid panel (SCHP) and radiation hybrid (RH) panel analysis. Sequences from an expressed sequence tag (EST) project in pig reproduction were examined and six genes and ESTs originally believed to map to HSA17 were selected for this study. The genes/ESTs were TATA box binding protein-associated factor (TAF2N/RBP56), alpha-2-plasmin inhibitor (SERPINF2/PLI), H3 histone family 3B (H3F3B), aminopeptidase puromycin sensitive (NPEPPS), an expressed sequence tag (ESTMI015) and P311 protein (P311). The SCHP analysis mapped five genes/ESTs (TAF2N, H3F3B, SERPINF2, NPEPPS and ESTMI015) to SSC12q11-q15 and SSC12p11-p15 with 100% concordance, and assigned P311 to SSC2 (1/2q24)-q29 with 100% concordance. Radiation hybrid analysis of all six genes confirmed the SCHP mapping results, with average retention frequency of 25%. Recent human sequence data demonstrated that P311 is actually located on HSA5q. As HSA5q and SSC2q show conserved syntenic regions predicted from bi-directional painting, our P311 mapping data is consistent with these results. An expanded comparative SSC12 RH map integrating the five new type I markers and 23 previously mapped loci was established using a LOD score threshold of 4.8. The gene order of the five genes/ESTs on the SSC12 framework RH map (H3F3B-ESTMI015-NPEPPS-TAF2N-SERPINF2) is identical to the HSA17 GB4 map but with inversion of the map as conventionally drawn. 相似文献