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381.
Daniel P. Cardinali Daniel E. Vigo 《Cellular and molecular life sciences : CMLS》2017,74(21):3941-3954
A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed. 相似文献
382.
E. Giacomelli C. L. Mummery M. Bellin 《Cellular and molecular life sciences : CMLS》2017,74(20):3711-3739
Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current literature clearly shows that hPSC-CMs recapitulate many molecular, cellular, and functional aspects of human heart pathophysiology and their responses to cardioactive drugs. Here, we provide a comprehensive overview of hPSC-CMs models that have been described to date and highlight their most recent and remarkable contributions to research on cardiovascular diseases and disorders with cardiac traits. We conclude discussing immediate challenges, limitations, and emerging solutions. 相似文献
383.
V. Le Fourn K. Gaplovska-Kysela B. Guhl R. Santimaria C. Zuber J. Roth 《Cellular and molecular life sciences : CMLS》2009,66(8):1434-1445
Little is known about the fate of machinery proteins of the protein quality control and endoplasmic reticulum(ER)-associated
degradation (ERAD). We investigated the degradation of the ERAD component EDEM1, which directs overexpressed misfolded glycoproteins
to degradation. Endogenous EDEM1 was studied since EDEM1 overexpression not only resulted in inappropriate occurrence throughout
the ER but also caused cytotoxic effects. Proteasome inhibitors had no effect on the clearance of endogenous EDEM1 in non-starved
cells. However, EDEM1 could be detected by immunocytochemistry in autophagosomes and biochemically in LC3 immuno-purified
autophagosomes. Furthermore, influencing the lysosome-autophagy pathway by vinblastine or pepstatin A/E64d and inhibiting
autophagosome formation by 3-methyladenine or ATGs short interfering RNA knockdown stabilized EDEM1. Autophagic degradation
involved removal of cytosolic Triton X-100-insoluble deglycosylated EDEM1, but not of EDEM1-containing ER cisternae. Our studies
demonstrate that endogenous EDEM1 in cells not stressed by the expression of a transgenic misfolded protein reaches the cytosol
and is degraded by basal autophagy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 15 January 2009; received after revision 16 February 2009; accepted 17 February 2009
V. Le Fourn, K. Gaplovska-Kysela: These authors equally contributed to this work. 相似文献
384.
A. Fridkin A. Penkner V. Jantsch Y. Gruenbaum 《Cellular and molecular life sciences : CMLS》2009,66(9):1518-1533
385.
R. P. Massengo-Tiassé J. E. Cronan 《Cellular and molecular life sciences : CMLS》2009,66(9):1507-1517
The enoyl-acyl carrier protein reductase (ENR) is the last enzyme in the fatty acid elongation cycle. Unlike most enzymes
in this essential pathway, ENR displays an unusual diversity among organisms. The growing interest in ENRs is mainly due to
the fact that a variety of both synthetic and natural antibacterial compounds are shown to specifically target their activity.
The primary anti-tuberculosis drug, isoniazid, and the broadly used antibacterial compound, triclosan, both target this enzyme.
In this review, we discuss the diversity of ENRs, and their inhibitors in the light of current research progress.
Received 3 November 2008; received after revision 5 December 2008; accepted 8 December 2008 相似文献
386.
I. Campia E. Gazzano G. Pescarmona D. Ghigo A. Bosia C. Riganti 《Cellular and molecular life sciences : CMLS》2009,66(9):1580-1594
Digoxin and ouabain are steroid drugs that inhibit the Na+/K+-ATPase, and are widely used in the treatment of heart diseases. They may also have additional effects, such as on metabolism
of steroid hormones, although until now no evidence has been provided about the effects of these cardioactive glycosides on
the synthesis of cholesterol. Here we report that digoxin and ouabain increased the synthesis of cholesterol in human liver
HepG2 cells, enhancing the activity and the expression of the
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of the cholesterol synthesis. This effect
was mediated by the binding of the sterol regulatory element binding protein-2 (SREBP-2) to the HMGCR promoter, and was lost
in cells silenced for SREBP-2 or loaded with increasing amounts of cholesterol. Digoxin and ouabain competed with cholesterol
for binding to the SREBP-cleavage-activating protein, and are critical regulators of cholesterol synthesis in human liver
cells.
Received 10 January 2009; received after revision 11 February 2009; accepted 6 March 2009 相似文献
387.
Berger W Steiner E Grusch M Elbling L Micksche M 《Cellular and molecular life sciences : CMLS》2009,66(1):43-61
The unique and evolutionary highly conserved major vault protein (MVP) is the main component of ubiquitous, large cellular
ribonucleoparticles termed vaults. The 100 kDa MVP represents more than 70% of the vault mass which contains two additional
proteins, the vault poly (ADP-ribose) polymerase (vPARP) and the telomerase-associated protein 1 (TEP1), as well as several
short untranslated RNAs (vRNA). Vaults are almost ubiquitously expressed and, besides chemotherapy resistance, have been implicated
in the regulation of several cellular processes including transport mechanisms, signal transmissions and immune responses.
Despite a growing amount of data from diverse species and systems, the definition of precise vault functions is still highly
complex and challenging. Here we review the current knowledge on MVP and vaults with focus on regulatory functions in intracellular
signal transduction and immune defence.
Received 27 June 2008; received after revision 25 July 2008; accepted 30 July 2008 相似文献
388.
Wolfs JL Comfurius P Bekers O Zwaal RF Balasubramanian K Schroit AJ Lindhout T Bevers EM 《Cellular and molecular life sciences : CMLS》2009,66(2):314-323
The exposure of phosphatidylserine (PS) at the cell surface plays a critical role in blood coagulation and serves as a macrophage
recognition moiety for the engulfment of apoptotic cells. Previous observations have shown that a high extracellular [K+] and selective K+ channel blockers inhibit PS exposure in platelets and erythrocytes. Here we show that the rate of PS exposure in erythrocytes
decreases by ~50% when the intracellular [K+] increases from 0 to physiological concentrations. Using resealed erythrocyte membranes, we further show that lipid scrambling
is inducible by raising the intracellular [Ca2+] and that K+ ions have a direct inhibitory effect on this process. Lipid scrambling in resealed ghosts occurs in the absence of cell shrinkage
and microvesicle formation, processes that are generally attributed to Ca2+-induced lipid scrambling in intact erythrocytes. Thus, opening of Ca2+-sensitive K+ channels causes loss of intracellular K+ that results in reduced intrinsic inhibitory effect of these ions on scramblase activity.
Received 11 September 2008; received after revision 17 October 2008; accepted 27 October 2008 相似文献
389.
Forecasting VaR models under Different Volatility Processes and Distributions of Return Innovations 下载免费PDF全文
This paper provides clear‐cut evidence that the out‐of‐sample VaR (value‐at‐risk) forecasting performance of alternative parametric volatility models, like EGARCH (exponential general autoregressive conditional heteroskedasticity) or GARCH, and Markov regime‐switching models, can be considerably improved if they are combined with skewed distributions of asset return innovations. The performance of these models is found to be similar to that of the EVT (extreme value theory) approach. The performance of the latter approach can also be improved if asset return innovations are assumed to be skewed distributed. The performance of the Markov regime‐switching model is considerably improved if this model allows for EGARCH effects, for all different volatility regimes considered. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
390.
V. Sala S. Bergerone S. Gatti S. Gallo A. Ponzetto C. Ponzetto T. Crepaldi 《Cellular and molecular life sciences : CMLS》2014,71(8):1439-1452
MicroRNAs (miRNAs) are natural, single-stranded, small RNA molecules which subtly control gene expression. Several studies indicate that specific miRNAs can regulate heart function both in development and disease. Despite prevention programs and new therapeutic agents, cardiovascular disease remains the main cause of death in developed countries. The elevated number of heart failure episodes is mostly due to myocardial infarction (MI). An increasing number of studies have been carried out reporting changes in miRNAs gene expression and exploring their role in MI and heart failure. In this review, we furnish a critical analysis of where the frontier of knowledge has arrived in the fields of basic and translational research on miRNAs in cardiac ischemia. We first summarize the basal information on miRNA biology and regulation, especially concentrating on the feedback loops which control cardiac-enriched miRNAs. A focus on the role of miRNAs in the pathogenesis of myocardial ischemia and in the attenuation of injury is presented. Particular attention is given to cardiomyocyte death (apoptosis and necrosis), fibrosis, neovascularization, and heart failure. Then, we address the potential of miR-diagnosis (miRNAs as disease biomarkers) and miR-drugs (miRNAs as therapeutic targets) for cardiac ischemia and heart failure. Finally, we evaluate the use of miRNAs in the emerging field of regenerative medicine. 相似文献