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991.
Catecholamine (CAT) release from chromaffin tissue plays an essential role in the fetus which develops in a low O2 environment (hypoxia). To address molecular mechanisms regulating CAT secretion in low O2, we exposed a fetal chromaffin-derived cell line (MAH cells) to chronic hypoxia (CHox; 2% O2, 24 h) and assessed gene expression using microarrays, quantitative RT-PCR, and western blot. CHox caused a dramatic ∼12× upregulation of adenosine A2a receptor (A2aR) mRNA, an effect critically dependent upon hypoxia-inducible factor (HIF)-2α which bound the promoter of the A2aR gene. In amperometric studies, acute hypoxia and high K+ (30 mM) evoked quantal CAT secretion that was enhanced after CHox, and further potentiated during simultaneous A2aR activation by adenosine. A2aR activation also enhanced stimulus-induced rise in intracellular Ca2+ in control, but not HIF-2α-deficient, MAH cells. Thus, A2aR, adenosine, and HIF-2α are key contributors to the potentiation of CAT secretion in developing chromaffin cells during chronic hypoxia. 相似文献
992.
Martínez-Abundis E Correa F Rodríguez E Soria-Castro E Rodríguez-Zavala JS Pacheco-Alvarez D Zazueta C 《Biochimica et biophysica acta》2011,1808(7):1888-1895
Several proteins that interact with cholesterol have a highly conserved sequence, corresponding to the cholesterol recognition/interaction amino acid consensus. Since cholesterol has been proposed to modulate both oligomerization and insertion of the pro-apoptotic protein BAX, we investigated the existence of such a motif in the BAX sequence. Residues 113 to 119 of the recombinant BAX α5-helix, LFYFASK, correspond with the sequence motif described for the consensus pattern, -L/V-(X)(1-5)-Y-(X)(1-5)-R/K. Functional characterization of the point mutations, K119A, Y115F, and L113A in BAX, was performed in liposomes supplemented with cholesterol, comparing binding, integration, and pore forming activities. Our results show that the mutations Y115F and L113A changed the cholesterol-dependent insertion observed in the wild type protein. In addition, substitutions in the BAX sequence modified the concentration dependency of carboxyfluorescein release in liposomes, although neither pore activity of the wild type or of any of the mutants significantly increased in cholesterol-enriched liposomes. Thus, while it is likely that the putative CRAC motif in BAX accounts for its enhanced insertion in cholesterol-enriched liposomes; the pore forming properties of BAX did not depend on cholesterol content in the membranes, albeit those mutations changed the pore channeling activity of the protein. 相似文献
993.
As members of the family of heme-dependent enzymes, the heme dioxygenases are differentiated by virtue of their ability to catalyze the oxidation of l-tryptophan to N-formylkynurenine, the first and rate-limiting step in tryptophan catabolism. In the past several years, there have been a number of important developments that have meant that established proposals for the reaction mechanism in the heme dioxygenases have required reassessment. This focused review presents a summary of these recent advances, written from a structural and mechanistic perspective. It attempts to present answers to some of the long-standing questions, to highlight as yet unresolved issues, and to explore the similarities and differences of other well-known catalytic heme enzymes such as the cytochromes P450, NO synthase, and peroxidases. 相似文献
994.
In this work, a novel strategy for the controlled fabrication of biomolecular stimulus responsive water-in-oil-in-water (W/O/W) multiple emulsion using the membrane emulsification process was investigated. The emulsions interface was functionalized with a biomolecule able to function as a receptor for a target compound. The interaction between the biomolecular receptor and target stimulus activated the release of bioactive molecules contained within the structured emulsion. A glucose sensitive emulsion was investigated as a model study case. Concanavalin A (Con A) was used as the biomolecular glucose sensor. Various physicochemical strategies for stimulus responsive materials formulation are available in literature, but the preparation of biomolecule-responsive emulsions has been explored for the first time in this paper. The development of novel drug delivery systems requires advanced and highly precise techniques to obtain their particular properties and targeting requirements. The present study has proven the flexibility and suitability of membrane emulsification for the preparation of stable and functional multiple emulsions containing Con A as interfacial biomolecular receptor able to activate the release of a bioactive molecule as a consequence of interaction with the glucose target molecule. The influence of emulsion interfacial composition and membrane emulsification operating conditions on droplets stability and functional properties have been investigated. The release of the bioactive molecule as a function of glucose stimulus and its concentration has been demonstrated. 相似文献
995.
996.
The disordered Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) modulates the dynamics and stability of the microtubule system and plays a crucial role in differentiation of oligodendrocytes. Here we first demonstrated by multinuclear NMR that the extended disordered segments are localized at the N- and C-terminals straddling a flexible region. We showed by affinity chromatography, fluorescence spectroscopy and circular dichroism that GTP binds to TPPP/p25 likely within the flexible region; neither positions nor intensities of the peaks in the assigned terminals were affected by GTP. In addition, we demonstrated that TPPP/p25 specifically hydrolyses GTP in an Mg(2+)-dependent manner. The GTPase activity is comparable with the intrinsic activities of small G proteins suggesting its potential role in multiple physiological processes. 相似文献
997.
Stuart Hunt Adam V. Jones Emma E. Hinsley Simon A. Whawell Daniel W. Lambert 《FEBS letters》2011,585(1):187
Alterations in the levels of molecules which interact with the extracellular matrix, such as integrins, are associated with invasion of oral squamous cell carcinomas (OSCC). The molecular mechanisms underlying dysregulation of integrin expression in OSCC, however, remain unclear. Here, we show that microRNA-124, a small non-coding RNA down-regulated in OSCC, is able to downregulate expression of integrin beta-1 (ITGB1) by interacting with its 3′ untranslated region. Over-expression of miR-124 attenuates endogenous ITGB1 expression and reduces the adherence and motility of OSCC cells, suggesting disruption of miR-124-mediated repression of ITGB1 may be a key factor in OSCC progression. 相似文献
998.
Wolánski M Wali R Tilley E Jakimowicz D Zakrzewska-Czerwinska J Herron P 《Journal of bacteriology》2011,193(5):1273-1275
We observed movies of replisome trafficking during Streptomyces coelicolor growth. A replisome(s) in the spore served as a replication center(s) until hyphae reached a certain length, when a tip-proximal replisome formed and moved at a fixed distance behind the tip at a speed equivalent to the extension rate of the tip. 相似文献
999.
Studies carried out in cultured cells have implicated modifiers of epigenetic reprogramming in the regulation of telomere
length, reporting elongation in cells that were null for DNA methyltransferase DNA methyltransferase 1 (Dnmt1), both de novo
DNA methyltransferases, Dnmt3a and Dnmt3b or various histone methyltransferases. To investigate this further, we assayed telomere
length in whole embryos or adult tissue from mice carrying mutations in four different modifiers of epigenetic reprogramming:
Dnmt1, DNA methyltransferase 3-like, structural maintenance of chromosomes hinge domain containing 1, and forkhead box O3a. Terminal restriction fragment analysis was used to compare telomere length in homozygous mutants, heterozygous mutants and
wild-type littermates. Contrary to expectation, we did not detect overall lengthening in the mutants, raising questions about
the role of epigenetic processes in telomere length in vivo. 相似文献
1000.
Noé López-Martínez Ma. Teresa Colinas-León Cecilia B. Peña-Valdivia Yolanda Salinas-Moreno Patricia Fuentes-Montiel Magdalena Biesaga Emma Zavaleta-Mejía 《Plant and Soil》2011,338(1-2):399-409
Chilli CM334 (Capsicum annuum L.) is resistant to Phytophthora capsici Leonian (Pc), but Nacobbus aberrans Thorne and Allen, 1944 (Na) broke down its resistance in plants previously infected by the nematode. Peroxidase (POD) and L-phenylalanine ammonia-lyase (PAL) activity, total soluble phenols (TSP) and chlorogenic acid concentration in CM334 plants inoculated with either or both pathogens (Na-Pc) were compared; also, the toxic effect of some phenolic acids on Na was tested in vitro. The highest POD activity (5.3 μM tetraguaiacol mg?1 protein min?1) was registered in plants inoculated only with Pc, while those inoculated only with Na showed the lowest (3.3 μM) (P?≤?0.05). PAL activity was 39.9 nM trans-cinnamic acid μg?1 protein min?1 in plants inoculated only with Pc, and it was lower (19.3 nM) and similar in non-inoculated plants or those with Na and with Na-Pc (P?≤?0.05). Usually, plants inoculated with Pc alone had higher contents of TSP (P?≤?0.05) (1.9 mg tannic acid g?1 dry matter) and plants inoculated with Na or Na-Pc had lower levels (0.8 and 0.9 mg) than those non-inoculated (1.3 mg). CM334 plants inoculated with Na showed a significant reduction (10–37% and 12–17%, in roots and leaves) in the concentration of chlorogenic acid as compared to the non-inoculated. Vanillic, trans-cinnamic, p-coumaric and syringic acids had greater nematicidal effects (P?≤?0.05) than chlorogenic acid in vitro. Apparently Na modified the defence responses in CM334 plants as POD and PAL activities and TSP and chlorogenic acid concentrations were reduced. 相似文献