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91.
Overexpression of heat shock proteins differentially modulates protein kinase C expression in rat neonatal cardiomyocytes 总被引:2,自引:0,他引:2 下载免费PDF全文
Previous studies have suggested that protein kinase C (PKC) is involved in heat shock protein (Hsp)-mediated cardioprotection. Therefore, we wanted to determine whether overexpression of Hsps modulates PKC expression, which will give us further insight into understanding the mechanism by which Hsps and PKC interact to protect cells from stress-induced injury. Specifically, we overexpressed the inducible form of Hsp70 (Hsp70i) or Hsp90 in rat neonatal cardiomyocytes and evaluated PKCdelta or PKCepsilon expression by immunoblotting and immunofluorescent confocal microscopy. Western analysis showed that overexpression of Hsp70i or Hsp90 decreased PKCepsilon expression. However, overexpression of Hsp70i or Hsp90 did not modify PKCdelta expression over control levels. Overexpression of constitutively active PKCdelta or PKCepsilon increased Hsp70i expression over control levels. The data suggest that overexpression of Hsps differentially modulates expression of PKC isoforms in rat neonatal cardiomyocytes. Furthermore, PKC may directly play a role in Hsp-mediated cardioprotection by upregulating Hsp70i expression. 相似文献
92.
Stress and radiation-induced activation of multiple intracellular signaling pathways 总被引:16,自引:0,他引:16
Dent P Yacoub A Contessa J Caron R Amorino G Valerie K Hagan MP Grant S Schmidt-Ullrich R 《Radiation research》2003,159(3):283-300
93.
Fiscella M Perry JW Teng B Bloom M Zhang C Leung K Pukac L Florence K Concepcion A Liu B Meng Y Chen C Elgin EC Kanakaraj P Kaufmann TE Porter J Cibotti R Mei Y Zhou J Chen G Roschke V Komatsoulis G Mansfield B Ruben S Sanyal I Migone TS 《Nature biotechnology》2003,21(3):302-307
A coordinated effort combining bioinformatic tools with high-throughput cell-based screening assays was implemented to identify novel factors involved in T-cell biology. We generated a unique library of cDNAs encoding predicted secreted and transmembrane domain-containing proteins generated by analyzing the Human Genome Sciences cDNA database with a combination of two algorithms that predict signal peptides. Supernatants from mammalian cells transiently transfected with this library were incubated with primary T cells and T-cell lines in several high-throughput assays. Here we describe the discovery of a T cell factor, TIP (T cell immunomodulatory protein), which does not show any homology to proteins with known function. Treatment of primary human and murine T cells with TIP in vitro resulted in the secretion of IFN-gamma, TNF-alpha, and IL-10, whereas in vivo TIP had a protective effect in a mouse acute graft-versus-host disease (GVHD) model. Therefore, combining functional genomics with high-throughput cell-based screening is a valuable and efficient approach to identifying immunomodulatory activities for novel proteins. 相似文献
94.
95.
Pathways involved in environmental sensing in trypanosomatids 总被引:6,自引:0,他引:6
Digenetic parasites, such as those of the order Kinetoplastida, must respond to extracellular and intracellular signals as they adapt to new environments within their different hosts. Evidence for signal transduction has been obtained for Trypanosoma brucei, T. cruzi and Leishmania, as reviewed here by Marilyn Parsons and Larry Ruben. Although the broad picture suggests similarities with the mammalian host, there are large gaps in our understanding of these processes; this probably contributes to a perception of differences. Nonetheless, current evidence suggests that the trypanosomatids might lack certain classes of signalling molecules found in other organisms. 相似文献
96.
Apolipoprotein E (apoE) is the primary recognition signal on triglyceride-rich lipoproteins responsible for interacting with low density lipoprotein (LDL) receptors and LDL receptor-related protein (LRP). It has been shown that lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) promote receptor-mediated uptake and degradation of very low density lipoproteins (VLDL) and remnant particles, possibly by directly binding to lipoprotein receptors. In this study we have investigated the requirement for apoE in lipase-stimulated VLDL degradation. We compared binding and degradation of normal and apoE-depleted human VLDL and apoE knockout mouse VLDL in human foreskin fibroblasts. Surface binding at 37 degrees C of apoE knockout VLDL was greater than that of normal VLDL by 3- and 40-fold, respectively, in the presence of LPL and HTGL. In spite of the greater stimulation of surface binding, lipase-stimulated degradation of apoE knockout mouse VLDL was significantly lower than that of normal VLDL (30, 30, and 80%, respectively, for control, LPL, and HTGL treatments). In the presence of LPL and HTGL, surface binding of apoE-depleted human VLDL was, respectively, 40 and 200% of normal VLDL whereas degradation was, respectively, 25 and 50% of normal VLDL. LPL and HTGL stimulated degradation of normal VLDL in a dose-dependent manner and by a LDL receptor-mediated pathway. Maximum stimulation (4-fold) was seen in the presence LPL (1 microgram/ml) or HTGL (3 microgram/ml) in lovastatin-treated cells. On the other hand, degradation of apoE-depleted VLDL was not significantly increased by the presence of lipases even in lovastatin-treated cells. Surface binding of apoE-depleted VLDL to metabolically inactive cells at 4 degrees C was higher in control and HTGL-treated cells, but unchanged in the presence of LPL. Degradation of prebound apoE-depleted VLDL was only 35% as efficient as that of normal VLDL. Surface binding of apoE knockout or apoE-depleted VLDL was to heparin sulfate proteoglycans because it was completely abolished by heparinase treatment. However, apoE appears to be a primary determinant for receptor-mediated VLDL degradation.Our studies suggest that overexpression of LPL or HTGL may not protect against lipoprotein accumulation seen in apoE deficiency. 相似文献
97.
Abundance, morphology and distribution of planktonic virus-like particles in two high-mountain lakes 总被引:5,自引:0,他引:5
Pina Sonia; Creus Andreu; Gonzaalez Nuria; Gironees Rosina; Felip Marisol; Sommaruga Ruben 《Journal of plankton research》1998,20(12):2413-2421
Direct counts of virus-like particles (VLP) by transmissionelectron microscopy revealed abundances of up to 3 x 107 ml1in the plankton of two remote high-mountain lakes in the Alpsand the Pyrenees. Most VLP were icosahedric without a tail,and with diameters between 40 and 90 nm, but very large oneswith diameters of up to 325 run were also observed. VLP outnumberedbacteria by a factor of 4.242.8 and bacterial cells wereinfected with large numbers (>50) of viral particles. Thisstudy constitutes the first report on aquatic viruses for alpinelakes and it suggests that they may be an important additionalsource of bacterial mortality in these systems. 相似文献
98.
Daniel Ajona Cristina Razquin Maria Dolores Pastor Maria Jose Pajares Javier Garcia Felipe Cardenal Michael Fleischhacker Maria Dolores Lozano Javier J. Zulueta Bernd Schmidt Ernest Nadal Luis Paz-Ares Luis M. Montuenga Ruben Pio 《PloS one》2015,10(3)
Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls) and the HUVR cohort (60 cases and 98 controls). A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort). Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95%CI = 0.71–0.94) and 0.67 (95%CI = 0.58–0.76) for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts). Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95%CI = 0.56–0.83). In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease. 相似文献
99.
100.
Endothelin-1 (ET-1) and bradykinin (BK) are endogenous peptides that signal through Gαq/11-protein coupled receptors (GPCRs) to produce nociceptor sensitization and pain. Both peptides activate phospholipase C to stimulate Ca2+ accumulation, diacylglycerol production, and protein kinase C activation and are rapidly desensitized via a G-protein receptor kinase 2-dependent mechanism. However, ET-1 produces a greater response and longer lasting nocifensive behavior than BK in multiple models, indicating a potentially divergent signaling mechanism in primary afferent sensory neurons. Using cultured sensory neurons, we demonstrate significant differences in both Ca2+ influx and Ca2+ release from intracellular stores following ET-1 and BK treatments. As intracellular store depletion may contribute to the regulation of other signaling cascades downstream of GPCRs, we concentrated our investigation on store-operated Ca2+ channels. Using pharmacological approaches, we identified transient receptor potential canonical channel 3 (TRPC3) as a dominant contributor to Ca2+ influx subsequent to ET-1 treatment. On the other hand, BK treatment stimulated Orai1 activation, with only minor input from TRPC3. Taken together, data presented here suggest that ET-1 signaling targets TRPC3, generating a prolonged Ca2+ signal that perpetuates nocifensive responses. In contrast, Orai1 dominates as the downstream target of BK receptor activation and results in transient intracellular Ca2+ increases and abridged nocifensive responses. 相似文献