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21.
ágnes Czikora Ibolya Rutkai Enik? T. Pásztor Andrea Szalai Róbert Pórszász Judit Boczán István édes Zoltán Papp Attila Tóth 《PloS one》2013,8(11)
Background and purpose
TRPV1 is expressed in sensory neurons and vascular smooth muscle cells, contributing to both pain perception and tissue blood distribution. Local desensitization of TRPV1 in sensory neurons by prolonged, high dose stimulation is re-engaged in clinical practice to achieve analgesia, but the effects of such treatments on the vascular TRPV1 are not known.Experimental approach
Newborn rats were injected with capsaicin for five days. Sensory activation was measured by eye wiping tests and plasma extravasation. Isolated, pressurized skeletal muscle arterioles were used to characterize TRPV1 mediated vascular responses, while expression of TRPV1 was detected by immunohistochemistry.Key results
Capsaicin evoked sensory responses, such as eye wiping (3.6±2.5 versus 15.5±1.4 wipes, p<0.01) or plasma extravasation (evans blue accumulation 10±3 versus 33±7 µg/g, p<0.05) were reduced in desensitized rats. In accordance, the number of TRPV1 positive sensory neurons in the dorsal root ganglia was also decreased. However, TRPV1 expression in smooth muscle cells was not affected by the treatment. There were no differences in the diameter (192±27 versus 194±8 µm), endothelium mediated dilations (evoked by acetylcholine), norepinephrine mediated constrictions, myogenic response and in the capsaicin evoked constrictions of arterioles isolated from skeletal muscle.Conclusion and implications
Systemic capsaicin treatment of juvenile rats evokes anatomical and functional disappearance of the TRPV1-expressing neuronal cells but does not affect the TRPV1-expressing cells of the arterioles, implicating different effects of TRPV1 stimulation on the viability of these cell types. 相似文献22.
Tibor Németh Adél Tóth Judit Szenzenstein Péter Horváth Joshua D. Nosanchuk Zsuzsanna Grózer Renáta Tóth Csaba Papp Zsuzsanna Hamari Csaba Vágv?lgyi Attila Gácser 《PloS one》2013,8(7)
The C. parapsilosis sensu lato group involves three closely related species, C. parapsilosis sensu stricto,
C
. orthopsilosis
and
C
. metapsilosis
. Although their overall clinical importance is dramatically increasing, there are few studies regarding the virulence properties of the species of the psilosis complex. In this study, we tested 63 C. parapsilosis sensu stricto, 12
C
. metapsilosis
and 18
C
. orthopsilosis
isolates for the ability to produce extracellular proteases, secrete lipases and form pseudohyphae. Significant differences were noted between species, with the
C
. metapsilosis
strains failing to secrete lipase or to produce pseudohyphae. Nine different clinical isolates each of C. parapsilosis sensu stricto,
C
. orthopsilosis
and
C
. metapsilosis
were co-cultured with immortalized murine or primary human macrophages. C. parapsilosis sensu stricto isolates showed a significantly higher resistance to killing by primary human macrophages compared to
C
. orthopsilosis
and
C
. metapsilosis
isolates. In contrast, the killing of isolates by J774.2 mouse macrophages did not differ significantly between species. However, C. parapsilosis sensu stricto isolates induced the most damage to murine and human macrophages, and
C
. metapsilosis
strains were the least toxic. Furthermore, strains that produced lipase or pseudohyphae were most resistant to macrophage-mediated killing and produced the most cellular damage. Finally, we used 9 isolates of each of the C. parapsilosis sensus lato species to examine their impact on the survival of
Galleria
mellonella
larvae. The mortality rate of
G
. mellonella
larvae infected with
C
. metapsilosis
isolates was significantly lower than those infected with C. parapsilosis sensu stricto or
C
. orthopsilosis
strains. Taken together, our findings demonstrate that
C
. metapsilosis
is indeed the least virulent member of the psilosis group, and also highlight the importance of pseudohyphae and secreted lipases during fungal-host interactions. 相似文献
23.
John A. Martignetti Lifeng Tian Dong Li Maria Celeste M. Ramirez Olga Camacho-Vanegas Sandra Catalina Camacho Yiran Guo Dina J. Zand Audrey M. Bernstein Sandra K. Masur Cecilia E. Kim Frederick G. Otieno Cuiping Hou Nada Abdel-Magid Ben Tweddale Denise Metry Jean-Christophe Fournet Eniko Papp Elizabeth W. McPherson Carrie Zabel Guy Vaksmann Cyril Morisot Brendan Keating Patrick M. Sleiman Jeffrey A. Cleveland David B. Everman Elaine Zackai Hakon Hakonarson 《American journal of human genetics》2013
24.
25.
Dukgyu Lee Tatsujiro Oka Beth Hunter Alison Robinson Sylvia Papp Kimitoshi Nakamura Wattamon Srisakuldee Barbara E. Nickel Peter E. Light Jason R. B. Dyck Gary D. Lopaschuk Elissavet Kardami Michal Opas Marek Michalak 《PloS one》2013,8(2)
Background
Calreticulin, a Ca2+-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart.Methodology/Principal Findings
We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca2+ signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca2+-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca2+-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin.Conclusions/Significance
We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca2+ handling genes, gap junction components and left ventricle remodeling. 相似文献26.
Sara Vandenwijngaert Peter Pokreisz Hadewich Hermans Hilde Gillijns Marijke Pellens Noortje A. M. Bax Giulia Coppiello Wouter Oosterlinck Agnes Balogh Zoltan Papp Carlijn V. C. Bouten Jozef Bartunek Jan D'hooge Aernout Luttun Erik Verbeken Marie Christine Herregods Paul Herijgers Kenneth D. Bloch Stefan Janssens 《PloS one》2013,8(3)
Background
The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC).Methodology/Principal Findings
In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dtmax and dP/dtmin with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro.Conclusions/Significance
Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target. 相似文献27.
Calreticulin affects fibronectin-based cell-substratum adhesion via the regulation of c-Src activity 总被引:2,自引:0,他引:2
Papp S Fadel MP Kim H McCulloch CA Opas M 《The Journal of biological chemistry》2007,282(22):16585-16598
Calreticulin is an endoplasmic reticulum Ca2+-storage protein, which influences gene expression and cell adhesion. In this study, we show that calreticulin induces fibronectin gene expression and matrix deposition, leading to differences in cell spreading and focal adhesion formation in cells differentially expressing calreticulin. We further show that these effects of calreticulin occur via a c-Src-regulated pathway and that c-Src activity is inversely related to calreticulin abundance. Since c-Src is an important regulator of focal contact turnover, we investigated the effect of c-Src inhibition on cells differentially expressing calreticulin. Inhibition of c-Src rescued the poorly adhesive phenotype of the calreticulin-underexpressing cells in that they became well spread, commenced formation of numerous focal contacts, and deposited a rich fibronectin matrix. Importantly, we show that c-Src activity is dependent on releasable Ca2+ from the endoplasmic reticulum, thus implicating Ca2+-sensitive pathways that are affected by calreticulin in cell-substratum adhesion. We propose that calreticulin affects fibronectin synthesis and matrix assembly via the regulation of fibronectin gene expression. In parallel, calcium-dependent effects of calreticulin on c-Src activity influence the formation and/or stability of focal contacts, which are instrumental in matrix assembly and remodeling. 相似文献
28.
Papp R Luk P Mullett WM Kwong E 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,858(1-2):282-286
A rapid LC-MS/MS method was developed and partially validated for the quantitation of montelukast in spiked sheep plasma. A total run time of 1.5 min was achieved using a short monolithic column and employing a rapid gradient. Sample preparation involved protein precipitation with twofold acetonitrile by volume during which a deuterated internal standard (montelukast D-6) was incorporated. The MRM transitions for montelukast and the deuterated internal standard were 586/422 and 592/427, respectively. A linear dynamic range of 0.25-500 ng/mL with a correlation coefficient of 0.9999 was achieved. Precision was below 5% at all levels except at the LOQ (0.36 ng/mL) which demonstrated an overall of R.S.D. of 8%. Post-column infusion experiments were performed with precipitated plasma matrix and showed minimal interference with the peaks of interest. 相似文献
29.
Gene expression dynamics in deer antler: mesenchymal differentiation toward chondrogenesis 总被引:6,自引:0,他引:6
Gyurján I Molnár A Borsy A Stéger V Hackler L Zomborszky Z Papp P Duda E Deák F Lakatos P Puskás LG Orosz L 《Molecular genetics and genomics : MGG》2007,277(3):221-235
Annual re-growth of deer antler represents a unique example of complete organ regeneration. Because antler mesenchymal cells
retain their embryonic capacity to develop into cartilage or bone, studying antler development provides a natural system to
follow gene expression changes during mesenchymal differentiation toward chondrogenic/osteogenic lineage. To identify novel
genes involved either in early events of mesenchymal cell specialization or in robust bone development, we have introduced
a 3 K heterologous microarray set-up (deer cDNA versus mouse template). Fifteen genes were differentially expressed; genes
for housekeeping, regulatory functions (components of different signaling pathways, including FGF, TGFβ, Wnt), and genes encoding
members of the Polycomb group were represented. Expression dynamics for genes are visualized by an expression logo. The expression
profile of the gene C21orf70 of unknown function is described along with the effects when over-expressed; furthermore the nuclear localization of the
cognate protein is shown. In this report, we demonstrate the particular advantage of the velvet antler model in bone research
for: (1) identification of mesenchymal and precartilaginous genes and (2) targeting genes upregulated in robust cartilage
development.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
30.
Postischemic calmodulin gene expression in the rat hippocampus 总被引:3,自引:0,他引:3
Palfi A Simonka JA Pataricza M Tekulics P Lepran I Papp G Gulya K 《Life sciences》2001,68(21):2373-2381