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- Fraqueza, Gil, et al.
(författare)
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Decavanadate, decaniobate, tungstate and molybdate interactions with sarcoplasmic reticulum Ca2+-ATPase : quercetin prevents cysteine oxidation by vanadate but does not reverse ATPase inhibition
- 2012
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 41:41, s. 12749-12758
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Tidskriftsartikel (refereegranskat)abstract
- Recently we demonstrated that the decavanadate (V-10) ion is a stronger Ca2+-ATPase inhibitor than other oxometalates, such as the isoelectronic and isostructural decaniobate ion, and the tungstate and molybdate monomer ions, and that it binds to this protein with a 1 : 1 stoichiometry. The V-10 interaction is not affected by any of the protein conformations that occur during the process of calcium translocation (i.e. E1, E1P, E2 and E2P) (Fraqueza et al., J. Inorg. Biochem., 2012). In the present study, we further explore this subject, and we can now show that the decaniobate ion, [Nb-10 = Nb10O28](6-), is a useful tool in deducing the interaction and the non-competitive Ca2+-ATPase inhibition by the decavanadate ion [V-10 = V10O28](6-). Moreover, decavanadate and vanadate induce protein cysteine oxidation whereas no effects were detected for the decaniobate, tungstate or molybdate ions. The presence of the antioxidant quercetin prevents cysteine oxidation, but not ATPase inhibition, by vanadate or decavanadate. Definitive V(IV) EPR spectra were observed for decavanadate in the presence of sarcoplasmic reticulum Ca2+-ATPase, indicating a vanadate reduction at some stage of the protein interaction. Raman spectroscopy clearly shows that the protein conformation changes that are induced by V-10, Nb-10 and vanadate are different from the ones induced by molybdate and tungstate monomer ions. Here, Mo and W cause changes similar to those by phosphate, yielding changes similar to the E1P protein conformation. The putative reduction of vanadium(V) to vanadium(IV) and the non-competitive binding of the V-10 and Nb-10 decametalates may explain the differences in the Raman spectra compared to those seen in the presence of molybdate or tungstate. Putting it all together, we suggest that the ability of V-10 to inhibit the Ca2+-ATPase may be at least in part due to the process of vanadate reduction and associated protein cysteine oxidation. These results contribute to the understanding and application of these families of mono-and polyoxometalates as effective modulators of many biological processes, particularly those associated with calcium homeostasis.
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- Iranmanesh, I., et al.
(författare)
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On-chip ultrasonic sample preparation for cellular and molecular diagnostics
- 2014
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Ingår i: 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014. - : Chemical and Biological Microsystems Society. - 9780979806476 ; , s. 1163-1165
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Konferensbidrag (refereegranskat)abstract
- In the present paper we combine for the first time kHz- and MHz-frequency ultrasonic actuation for on-chip size-based isolation, up-concentration and lysis of cells. As proof of concept, we demonstrate MHz-frequency ultrasonic isolation and trapping of ∼10-μm (RH-30) cancer cells from ∼5-μm RBCs, and we investigate the kHz-frequency ultrasonic lysis effect on isolated cancer cells.
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- Ohlin, C. Andre, et al.
(författare)
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Rates of Water Exchange for Two Cobalt(II) Heteropolyoxotungstate Compounds in Aqueous Solution
- 2011
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 17:16, s. 4408-4417
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Tidskriftsartikel (refereegranskat)abstract
- Polyoxometalate ions are used as ligands in water-oxidation processes related to solar energy production. An important step in these reactions is the association and dissociation of water from the catalytic sites, the rates of which are unknown. Here we report the exchange rates of water ligated to Co-II atoms in two polyoxotungstate sandwich molecules using the O-17-NMR-based Swift-Connick method. The compounds were the [Co-4(H2O)(2)(B-alpha-PW9O34)(2)](10-) and the larger alpha beta beta alpha-[Co-4(H2O)(2)(P2W15O56)(2)](16-) ions, each with two water molecules bound trans to one another in a Co-II sandwich between the tungstate ligands. The clusters, in both solid and solution state, were characterized by a range of methods, including NMR, EPR, FT-IR, UV-Vis, and EXAFS spectroscopy, ESI-MS, single-crystal Xray crystallography, and potentiometry. For [Co-4(H2O)(2)(B-alpha-PW9O34)(2)](10-) at pH 5.4, we estimate: k(298) = 1.5(5) +/- 0.3 x 10(6) s(-1), Delta H-not equal = 39.8 +/- 0.4 kJ mol(-1), Delta S-not equal = + 7.1 +/- 1.2 J mol(-1)K(-1) and Delta V-not equal = 5.6 +/- 1.6 cm(3)mol(-1). For the Wells-Dawson sandwich cluster (alpha beta beta alpha-[Co-4(H2O)(2)(P2W15O56)(2)](16-)) at pH 5.54, we find: k(298) = 1.6(2) +/- 0.3 x 10(6)s(-1), Delta H-not equal = 27.6 +/- 0.4 kJ mol(-1) Delta S-not equal = -33 +/- 1.3 J mol(-1)K(-1) and Delta V-not equal = 2.2 +/- 1.4 cm(3)mol(-1) at pH 5.2. The molecules are clearly stable and monospecific in slightly acidic solutions, but dissociate in strongly acidic solutions. This dissociation is detectable by EPR spectroscopy as S=3/2 Co-II species (such as the [Co(H2O)(6)](2+) monomer ion) and by the significant reduction of the Co-Co vector in the XAS spectra.
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- Ohlin, Elisabet, et al.
(författare)
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Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia.
- 2011
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 134, s. 2339-2357
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis and increased permeability of the blood-brain barrier have been reported to occur in animal models of Parkinson's disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood-brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson's disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson's disease.
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- Aureliano, M., et al.
(författare)
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Decavanadate in vitro and in vivo effects : facts and opinions
- 2014
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Ingår i: Journal of Inorganic Biochemistry. - : Elsevier BV. - 0162-0134 .- 1873-3344. ; 137, s. 123-130
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Tidskriftsartikel (refereegranskat)abstract
- This review covers recent advances in the understanding of the in vitro and in vivo effects of decavanadate, (V10O28)(6-), particularly in mitochondria. In vivo toxicological studies involving vanadium rarely account for the fact that under physiological conditions some vanadium may be present in the form of the decavanadate ion, which may behave differently from ortho- and metavanadates. It has for example been demonstrated that vanadium levels in heart or liver mitochondria are increased upon decavanadate exposure. Additionally, in vitro studies have shown that mitochondrial depolarization (IC50, 40 nM) and oxygen consumption (IC50, 99 nM) are strongly affected by decavanadate, which causes reduction of cytochrome b (complex III). We review these recent findings which together suggest that the observed cellular targets, metabolic pathway and toxicological effects differ according to the species of vanadium present. Finally, the toxicological effects of decavanadate depend on several factors such as the mode of administration, exposure time and type of tissue. (C) 2014 Elsevier Inc. All rights reserved.
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- Bergenzaun, L., et al.
(författare)
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Mitral annular Plane Systolic Excursion (Mapse) in Shock : a Valuable Echocardiographic Parameter in Intensive Care Patients
- 2013
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Ingår i: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 39, s. S393-S393
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION. Assessing left ventricular (LV) dysfunction by echocardiography in ICU patients is common. In patients with cardiovascular disease mitral annular plane sys- tolic excursion (MAPSE) is known to be more sensitive in detecting abnormalities in LV function at an early stage, easily obtainable and related to prognosis. OBJECTIVES. The aim of this study was to investigate MAPSE in critically ill patients with shock and its relation to LV systolic and diastolic function, myocardial injury and to outcome. METHODS. In a prospective, observational, cohort study we enrolled 50 patients with SIRS and shock despite fluid resuscitation. Transthoracic echocardiography (TTE) mea- suring LV systolic and diastolic function was performed within 12 h after admission and daily for a 7-day observation period. TTE and laboratory measurements (high-sensitive troponin T (hsTNT), B-natriuretic peptide [BNP]) were related to 28-day mortality. Spearman rank correlation was used. RESULTS. MAPSE on day 1 correlated significantly with LV ejection fraction (LVEF), tissue Doppler indices of LV diastolic function (e ́ , E/e ́ ) and hsTNT whereas LVEF did not correlate significantly with any marker of LV diastolic function or myocardial injury; tissue Doppler of LV systolic function (TDIs) correlated significantly with LVEF and e ́ (Table 1). Compared to survivors, non-survivors had a significantly lower MAPSE (8 [IQR 7.5–11] versus 11 [IQR 8.9–13] mm; p = 0.028). Other univariate predictors were age (p = 0.033), hsTNT (p = 0.014) and Sequential Organ Failure Assessment (SOFA) scores (p = 0.007). By multivariate analysis MAPSE (OR 0.6 (95 % CI 0.5–0.9) p = 0.015) and SOFA score (OR 1.6 (95 % CI 1.1–2.3) p = 0.018) were identified as independent predictors of mor- tality. Daily measurements showed that MAPSE, as sole echocardiographic marker, was significantly lower in most days in non-survivors (p \ 0.05 at day 1–2, 4–6). CONCLUSIONS. MAPSE seemed to reflect LV systolic and diastolic function as well as myocardial injury in critically ill patients with shock. The combination of MAPSE and SOFA added to the predictive value for 28-day mortality
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