Effects of statins on the secretion of human serum albumin in cultured HepG2 cells

Statins reduce cholesterol biosynthesis by inhibiting HMG-CoA reductase and thereby lower total cholesterol and LDL cholesterol levels in serum, which in turn lower the incidence of cardiovascular disease (CVD). Statins are also known to modulate various cellular functions such as gene expression, cell proliferation, and programmed cell death through inhibition of downstream intermediates in cholesterol synthesis. In this study, we have investigated the possible effects of statins on the secretion of serum albumin from cultured HepG2 cells since high levels of serum albumin are associated with reduced risks for CVD and statins are effective in lowering the risk of CVD through other effects in addition to their effects on serum total cholesterol and LDL cholesterol levels, known as pleiotropic effects. Our results showed that simvastatin increased HSA secretion up to 32.3% compared to the control group. Among 3 statin analogs we tested, simvastatin exhibited the highest stimulatory effects on HSA secretion compared to the control group. Our study also showed that the increased HSA secretions from HepG2 cells by simvastatin treatments were due to the increased rate of HSA synthesis, not due to the reduced posttranslational degradation rate of HSA. Our finding suggests another added benefit of statins' treatments in preventing CVD through stimulation of HSA biosynthesis

Probing scrambling using statistical correlations between randomized measurements

We propose and analyze a protocol to study quantum information scrambling using statistical correlations between measurements, which are performed after evolving a quantum system from randomized initial states. We prove that the resulting correlations precisely capture the so-called out-of-time-ordered correlators and can be used to probe chaos in strongly-interacting, many-body systems. Our protocol requires neither reversing time evolution nor auxiliary degrees of freedom, and can be realized in state-of-the-art quantum simulation experiments.Comment: This version v2 (8 pages, 7 figures) includes important new results compared to our original submission. (1) We present a protocol and corresponding mathematical proof to access OTOCs with local operations, and which can be realized in quantum simulation experiments with available technology. (2) We illustrate the realization of the protocols with different examples for Hubbard and spin model

Insulinoma, a rare neuroendocrine tumor: a case report.

We report a case of Insulinoma, a rare neuroendocrine tumor with an incidence of approximately four per 5 million. This case demonstrates the characteristic clinical, biochemical and histological features of an insulinoma, a rare benign neuroendocrine tumor where early recognition is important to ensure proper surgical treatment and prevent serious adverse consequences

Comparative binding character of two general anaesthetics for sites on human serum albumin.

Propofol and halothane are clinically used general anaesthetics, which are transported primarily by HSA (human serum albumin) in the blood. Binding characteristics are therefore of interest for both the pharmacokinetics and pharmacodynamics of these drugs. We characterized anaesthetic-HSA interactions in solution using elution chromatography, ITC (isothermal titration calorimetry), hydrogen-exchange experiments and geometric analyses of high-resolution structures. Binding affinity of propofol to HSA was determined to have a K(d) of 65 microM and a stoichiometry of approx. 2, whereas the binding of halothane to HSA showed a K(d) of 1.6 mM and a stoichiometry of approx. 7. Anaesthetic-HSA interactions are exothermic, with propofol having a larger negative enthalpy change relative to halothane. Hydrogen-exchange studies in isolated recombinant domains of HSA showed that propofol-binding sites are primarily found in domain III, whereas halothane sites are more widely distributed. Both location and stoichiometry from these solution studies agree with data derived from X-ray crystal-structure studies, and further analyses of the architecture of sites from these structures suggested that greater hydrophobic contacts, van der Waals interactions and hydrogen-bond formation account for the stronger binding of propofol as compared with the less potent anaesthetic, halothane

Denitrosation of N-acetyl-nitroso-Trp (NANT) by glutathione (GSH).

<p>The decomposition of NANT (100 µM) was followed spectrophotometrically at 335 nm upon incubation with increasing concentrations of GSH in 100 mM phosphate buffer (pH 7.4) containing 100 µM DTPA. NANT decay followed apparent first order kinetics and k_obs for NANT decomposition was plotted as a function of [GSH]. The values represent the mean ± SEM (n = 4).</p

Truncated human serum albumin retains general anaesthetic binding activity

Multiple binding sites for anaesthetics in HSA (human serum albumin) make solution studies difficult to interpret. In the present study, we expressed the wild-type HSA domain 3 (wtHSAd3), a peptide with two known anaesthetic binding sites in a yeast expression system. We also expressed a site-directed mutant of domain 3 (Y411Wd3). The stability and secondary structure of the constructed fragments were determined by HX (hydrogen–tritium exchange) and CD spectroscopy. The binding of two general anaesthetics, 2-bromo-2-chloro-1,1,1-trifluoroethane and propofol, to wtHSAd3 and Y411Wd3 was determined using isothermal titration calorimetry, HX and intrinsic tryptophan fluorescence quenching. Although the expressed fragments are less stable than intact wtHSA as indicated by both CD and HX, they retain the secondary structure and anaesthetic-binding characteristics of an intact HSA molecule, but with fewer binding sites. Y411Wd3 had decreased affinity for propofol but not for 2-bromo-2-chloro-1,1,1-trifluoroethane, consistent with steric hindrance. Retention of structural features and anaesthetic binding properties with fewer binding sites in this truncated protein provide feasibility for using scaled-down models of otherwise intractable systems to gain an understanding of anaesthetic binding requirements and binding–stability relationships

Validation of nitrosamine determination by tri-iodide-based chemiluminescence assay.

<p>(<b>A</b>), Flow chart for the determination of nitroso species using the tri-iodide chemiluminescence assay. Details may be found under <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014400#s4" target="_blank">Materials and Methods</a>. (<b>B</b>), N-acetyl-nitroso-Trp (NANT, 10 µM) was preincubated with HgCl₂ or NEM in the presence of acidified sulfanilamide. The samples were then quantified by gas phase chemiluminescence as described under <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014400#s4" target="_blank">Materials and Methods</a>. The values represent the mean ± SEM (n = 3). (C), Stock solutions of GSNO and NANT of known concentrations were diluted and mixed together in 100 mM phosphate buffer containing DTPA (100 µM) and nitrite (40 µM) to obtain a final concentration of 5 µM for each compound. Concentrations were immediately determined using the same tri-iodide based chemiluminescence assay (n = 3, mean ± SEM).</p