74 research outputs found
Multiple quantum filtered <sup>23</sup>Na NMR in the Langendorff perfused mouse heart:Ratio of triple/double quantum filtered signals correlate with [Na]<sub>i</sub>
AbstractWe investigate the potential of multiple quantum filtered (MQF) 23Na NMR to probe intracellular [Na]i in the Langendorff perfused mouse heart. In the presence of Tm(DOTP) shift reagent the triple quantum filtered (TQF) signal originated largely from the intracellular sodium pool with a 32±6% contribution of the total TQF signal arising from extracellular sodium, whilst the rank 2 double-quantum filtered signal (DQF), acquired with a 54.7° flip-angle pulse, originated exclusively from the extracellular sodium pool. Given the different cellular origins of the 23Na MQF signals we propose that the TQF/DQF ratio can be used as a semi-quantitative measure of [Na]i in the mouse heart. We demonstrate a good correlation of this ratio with [Na]i measured with shift reagent at baseline and under conditions of elevated [Na]i. We compare the measurements of [Na]i using both shift reagent and TQF/DQF ratio in a cohort of wild type mouse hearts and in a transgenic PLM3SA mouse expressing a non-phosphorylatable form of phospholemman, showing a modest but measurable elevation of baseline [Na]i. MQF filtered 23Na NMR is a potentially useful tool for studying normal and pathophysiological changes in [Na]i, particularly in transgenic mouse models with altered Na regulation
Reduction of apoptosis and preservation of mitochondrial integrity under ischemia/reperfusion injury is mediated by estrogen receptor β
Doxorubicin-induced chronic dilated cardiomyopathy—the apoptosis hypothesis revisited
The chemotherapeutic agent doxorubicin (DOX) has significantly increased survival rates of pediatric and adult cancer patients. However, 10% of pediatric cancer survivors will 10–20 years later develop severe dilated cardiomyopathy (DCM), whereby the exact molecular mechanisms of disease progression after this long latency time remain puzzling. We here revisit the hypothesis that elevated apoptosis signaling or its increased likelihood after DOX exposure can lead to an impairment of cardiac function and cause a cardiac dilation. Based on recent literature evidence, we first argue why a dilated phenotype can occur when little apoptosis is detected. We then review findings suggesting that mature cardiomyocytes are protected against DOX-induced apoptosis downstream, but not upstream of mitochondrial outer membrane permeabilisation (MOMP). This lack of MOMP induction is proposed to alter the metabolic phenotype, induce hypertrophic remodeling, and lead to functional cardiac impairment even in the absence of cardiomyocyte apoptosis. We discuss findings that DOX exposure can lead to increased sensitivity to further cardiomyocyte apoptosis, which may cause a gradual loss in cardiomyocytes over time and a compensatory hypertrophic remodeling after treatment, potentially explaining the long lag time in disease onset. We finally note similarities between DOX-exposed cardiomyocytes and apoptosis-primed cancer cells and propose computational system biology as a tool to predict patient individual DOX doses. In conclusion, combining recent findings in rodent hearts and cardiomyocytes exposed to DOX with insights from apoptosis signal transduction allowed us to obtain a molecularly deeper insight in this delayed and still enigmatic pathology of DC
Endogenous CCL2 neutralization restricts HIV-1 replication in primary human macrophages by inhibiting viral DNA accumulation
Changes in Intracellular Na+ following Enhancement of Late Na+ Current in Virtual Human Ventricular Myocytes
The slowly inactivating or late Na+ current, INa-L, can contribute to the initiation of both atrial and ventricular rhythm disturbances in the human heart. However, the cellular and molecular mechanisms that underlie these pro-arrhythmic influences are not fully understood. At present, the major working hypothesis is that the Na+ influx corresponding to I(Na-L)significantly increases intracellular Na+, [Na]; and the resulting reduction in the electrochemical driving force for Na+ reduces and (may reverse) Na+/Ca2+ exchange. These changes increase intracellular Ca2+, [Ca2+]; which may further enhance I(Na-L)due to calmodulindependent phosphorylation of the Na+ channels. This paper is based on mathematical simulations using the O'Hara et al (2011) model of baseline or healthy human ventricular action potential waveforms(s) and its [Ca2(+)]; homeostasis mechanisms. Somewhat surprisingly, our results reveal only very small changes (<= 1.5 mM) in [Na] even when INa-L is increased 5-fold and steady-state stimulation rate is approximately 2 times the normal human heart rate (i.e. 2 Hz). Previous work done using well-established models of the rabbit and human ventricular action potential in heart failure settings also reported little or no change in [Na] when I(Na-L)was increased. Based on our simulations, the major short-term effect of markedly augmenting I(Na-L)is a significant prolongation of the action potential and an associated increase in the likelihood of reactivation of the L-type Ca2+ current, Ica-L. Furthermore, this action potential prolongation does not contribute to [Na]; increase.This work was supported by (i) the "VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica" from the Ministerio de Economia y Competitividad of Spain (grant number TIN2012-37546-C03-01) and the European Commission (European Regional Development Funds-ERDF-FEDER), (ii) by the Direccion General de Politica Cientifica de la Generalitat Valenciana (grant number GV/2013/119), and by (iii), Programa Prometeo (PROMETEO/2016/088) de la Conselleria d'Educacio Formacio I Ocupacio, Generalitat Valenciana. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.K Cardona; Trénor Gomis, BA.; W Giles (2016). Changes in Intracellular Na+ following Enhancement of Late Na+ Current in Virtual Human Ventricular Myocytes. PLoS ONE. 11(11). https://doi.org/10.1371/journal.pone.0167060S111
Molecular Structures and Electronic Structures of Transition-Metal Mixed-Sandwich Complexes, [CpFe(II)(PhX)](+1) and Ferrocene
The local structures of the transition-metal mixed-sandwich complexes, [CpFe(Il)(PhX)](+1), (Cp =η5-
cyclopentadienyl ; PhX =η6-benzene and its derivatives), have been studied by EXAFS and density-functional theory (DFT).
Fe K-edge EXAFS spectra were measured at 10K and analysed by a two-shell model, and DFT calculations were made to predict
more detailed molecular structures. Both methods give the Fe-C distance of ferrocene in good agreement with electron
diffraction in gas phase. For the mixed-sandwich complexes, EXAFS and DFT provide similar structures that the Fe-C
distance in the Ph-pyramid is slightly longer than that in the Cp-pyramid for all the derivatives except the
[CpFe(C6(CH3)6)](+) complex. It is found by DFT that the Fe-C(X) distance in the PhX-pyramid changes depending on
whether the substituent X is an electron donnor or an electron acceptor. We discuss the dependence from the valence MO's
and the Mulliken population analysis
APOBEC3G and G-to-A hypermutation in Asian children with different HIV/AIDS disease progression
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