Division of Nephrology, Hypertension, and Transplantation, Department of Medicine, University of Florida, Gainesville, Florida
Submitted 4 December 2006
; accepted in final form 5 April 2007
Uric ...acid is considered a major antioxidant in human blood that may protect against aging and oxidative stress. Despite its proposed protective properties, elevated levels of uric acid are commonly associated with increased risk for cardiovascular disease and mortality. Furthermore, recent experimental studies suggest that uric acid may have a causal role in hypertension and metabolic syndrome. All these conditions are thought to be mediated by oxidative stress. In this study we demonstrate that differentiation of cultured mouse adipocytes is associated with increased production of reactive oxygen species (ROS) and uptake of uric acid. Soluble uric acid stimulated an increase in NADPH oxidase activity and ROS production in mature adipocytes but not in preadipocytes. The stimulation of NADPH oxidase-dependent ROS by uric acid resulted in activation of MAP kinases p38 and ERK1/2, a decrease in nitric oxide bioavailability, and an increase in protein nitrosylation and lipid oxidation. Collectively, our results suggest that hyperuricemia induces redox-dependent signaling and oxidative stress in adipocytes. Since oxidative stress in the adipose tissue has recently been recognized as a major cause of insulin resistance and cardiovascular disease, hyperuricemia-induced alterations in oxidative homeostasis in the adipose tissue might play an important role in these derangements.
redox signaling; nitric oxide; reactive oxygen species
Address for reprint requests and other correspondence: Y. Y. Sautin, Division of Nephrology, Hypertension, and Transplantation, Dept. of Medicine, Univ. of Florida, PO Box 100224, Gainesville, FL 32610-0224 (e-mail: sautiyy{at}medicine.ufl.edu )
Abstract
We present a new study of the Z Cam-type eclipsing cataclysmic variable AY Piscium with the aim of determining the fundamental parameters of the system and the structure of the accretion ...flow therein. We use time-resolved photometric observations supplemented by spectroscopy in the standstill, to which we applied our light-curve modeling techniques and the Doppler tomography method, to update system parameters. We found that the system has a massive white dwarf
M
WD
= 0.90(4)
M
☉
, a mass ratio
q
= 0.50(3), and the effective temperature of a secondary
T
2
= 4100(50) K. The system inclination is
i
= 74.°8(7). The orbital period of the system
P
orb
= 0.217320523(8) day is continuously increasing at a rate of
P
̇
orb
=
+
7.6
(
5
)
×
10
−
9
day yr
−1
. The mass-transfer rate varies between 2.4 × 10
−10
M
⊙
yr
−1
in quiescence up to 1.36 × 10
−8
M
⊙
yr
−1
in outburst. The accretion disk transitions from the cooler, flared, steady-state disk to a warmer state with a practically constant and relatively high disk height. The mass-transfer rate is about 1.6 × 10
−9
M
⊙
yr
−1
in the standstill. The Balmer emission lines show a multicomponent structure similar to that observed in long-orbital-period nova-like systems. Out of standstill, the system exhibits outburst bimodality, with long outbursts being more prominent. We conclude that the Balmer emission lines in AY Psc are formed by the combination of radiation from the irradiated surface of the secondary, from the outflow zone, and from winds originating in the bright spot and the disk’s inner part.
The black hole (BH) candidate SWIFT J1753.5−0127 has remained active since the onset of its 2005 outburst. Emission lines in the optical spectrum were observed at the very beginning of the outburst, ...but since then the spectrum has been featureless making a precise BH mass estimation impossible. Here we present results from our optical and ultraviolet (UV) observations of SWIFT J1753.5−0127 taken in 2012–2013. Our new observations show extremely broad, double-peaked emission lines in the optical and UV spectra. The optical data also show narrow absorption and emission features with nearly synchronous and significant Doppler motions. A radial velocity study of these lines which we associate with the secondary star, yields a semi-amplitude of K
2 = 382 km s−1. A time series analysis of the spectral and photometric data revealed a possible orbital periodicity of 2.85 h, significantly shorter than the reported 3.2 h periodic signal by Zurita et al. The observed variability properties argue against a low orbital inclination angle and we present several observational arguments in favour of the BH interpretation. However, the measured radial velocity semi-amplitude of the donor star and the short orbital period imply that SWIFT J1753.5−0127 has one of the lowest measured mass function for a BH in a low-mass X-ray binary. We show that the compact object mass in excess of 5 M⊙ is highly improbable. Thus, SWIFT J1753.5−0127 is a BH binary that has one of the shortest orbital period and hosts probably one of the smallest stellar mass BH found to date.
IRAS 22150+6109 – a young B-type star with a large disc Zakhozhay, Olga V; Miroshnichenko, Anatoly S; Kuratov, Kenesken S ...
Monthly notices of the Royal Astronomical Society,
06/2018, Volume:
477, Issue:
1
Journal Article
Peer reviewed
Open access
Abstract
We present the results of a spectroscopic analysis and spectral energy distribution (SED) modelling of the optical counterpart of the infrared source IRAS 22150+6109. The source was ...suggested to be a Herbig Be star located in the star-forming region L 1188. Absorption lines in the optical spectrum indicate a spectral type B3, while weak Balmer emission lines reflect the presence of a circumstellar gaseous disc. The star shows no excess radiation in the near-infrared spectral region and a strong excess in the far-infrared that we interpret as radiation from a large disc, the inner edge of which is located very far from the star (550 au) and does not attenuate its radiation. We conclude that IRAS 22150+6109 is an intermediate-mass star that is currently undergoing a short pre-main-sequence evolutionary stage.
The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn ...syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, we hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome. Four sets of experiments were performed. First, pair-feeding studies showed that fructose, and not dextrose, induced features (hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) of metabolic syndrome. Second, in rats receiving a high-fructose diet, the lowering of uric acid with either allopurinol (a xanthine oxidase inhibitor) or benzbromarone (a uricosuric agent) was able to prevent or reverse features of metabolic syndrome. In particular, the administration of allopurinol prophylactically prevented fructose-induced hyperinsulinemia (272.3 vs.160.8 pmol/l, P < 0.05), systolic hypertension (142 vs. 133 mmHg, P < 0.05), hypertriglyceridemia (233.7 vs. 65.4 mg/dl, P < 0.01), and weight gain (455 vs. 425 g, P < 0.05) at 8 wk. Neither allopurinol nor benzbromarone affected dietary intake of control diet in rats. Finally, uric acid dose dependently inhibited endothelial function as manifested by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid.
κ Draconis is a binary system with a classical Be star as the primary component. Its emission-line spectrum consists of hydrogen lines, notably the Hα line with peak intensity ratio (V/R) variations ...phase-locked with the orbital period P = 61.55 days. Among binaries demonstrating the Be phenomenon, κ Dra stands out as one of a few systems with a discernible mass of its secondary component. Based on more than 200 spectra obtained in 2014–2023, we verified the physical parameters and constructed the mass function. We used part of these data obtained in 2014–2021 to investigate regions in the circumstellar disk of the primary component that emit the Hα line using the Doppler tomography method. The results show that the disk has a non-uniform density distribution with a prominent enhancement at Vy ≈ 99 km s−1 and Vx≈−6 km s−1 that corresponds to a cloud-like source of the double-peaked Hα line profile. We argue that this enhancement’s motion is responsible for the periodic variations in the Hα V/R ratio, which is synchronised in orbital phase with the radial velocity (RV) of absorption lines from the atmosphere of the primary component.
Nitrite (NO2(-)), a dietary constituent and nitric oxide (NO) oxidation product, mediates cardioprotection after ischaemia/reperfusion (I/R) in a number of animal models when administered during ...ischaemia or as a pre-conditioning agent hours to days prior to the ischaemic episode. When present during ischaemia, the reduction of nitrite to bioactive NO by deoxygenated haem proteins accounts for its protective effects. However, the mechanism of nitrite-induced pre-conditioning, a normoxic response which does not appear to require reduction of nitrite to NO, remains unexplored.
Using a model of hypoxia/reoxygenation (H/R) in cultured rat H9c2 cardiomyocytes, we demonstrate that a transient (30 min) normoxic nitrite treatment significantly attenuates cell death after a hypoxic episode initiated 1 h later. Mechanistically, this protection depends on the activation of protein kinase A, which phosphorylates and inhibits dynamin-related protein 1, the predominant regulator of mitochondrial fission. This results morphologically, in the promotion of mitochondrial fusion and functionally in the augmentation of mitochondrial membrane potential and superoxide production. We identify AMP kinase (AMPK) as a downstream target of the mitochondrial reactive oxygen species (ROS) generated and show that its oxidation and subsequent phosphorylation are essential for cytoprotection, as scavenging of ROS prevents AMPK activation and inhibits nitrite-mediated protection after H/R. The protein kinase A-dependent protection mediated by nitrite is reproduced in an intact isolated rat heart model of I/R.
These data are the first to demonstrate nitrite-dependent normoxic modulation of both mitochondrial morphology and function and reveal a novel signalling pathway responsible for nitrite-mediated cardioprotection.
Activated arginase has been implicated in many diseases including cancer, immune cell dysfunction, infections, and vascular disease. Enhanced arginase activity has been reported in lungs of patients ...with pulmonary artery hypertension. We used hypoxia as a model for pulmonary hypertension and studied the effect of exposure to hypoxia on arginase activity in human lung microvascular endothelial cells (HMVEC). Hypoxia induces upregulation of arginase activity as well as mRNA and protein levels of arginase II (Arg II), the only arginase isoform we were able to identify in HMVEC. In endothelial cells, arginase shares and competes for the substrate l-arginine with nitric oxide (NO) synthase (NOS). Through regulation of substrate availability for NOS, arginase is able to modulate NO production. To evaluate the role of Arg II in regulation of NO production under hypoxia, we compared NO output (RFL-6 reporter assay) in cells with normal and silenced Arg II. Exposure to hypoxia led to an increase in NO levels produced by HMVEC. Inhibition of Arg II by specific small interfering RNA or by the pharmacological inhibitor BEC additionally enhanced the levels of NO. Another possible role for activated arginase is involvement in regulation of cell proliferation. However, we showed that hypoxia decreased cell proliferation and upregulated Arg II did not have an effect on cell proliferation. Since hypoxia-inducible factors (HIF) are a family of transcriptional factors activated by hypoxia, we tested the possibility of involvement of HIF-1 and HIF-2 in regulation of Arg II under hypoxia. The silencing of HIF-2 but not HIF-1 prevented the activation of Arg II by hypoxia.
As the depth of mining increases, attention to the preservation of mine workings and mining blasting is steadily growing. Technological methods of effective mineral development are often limited by ...dynamic blasting impact causing short-period fluctuations in the rock mass. Therefore, correct explosion impact identification, to a great extent, determines effective mining trends. Some results of researches for minimum blasting impact on mining workings are given in the article. Calculation of safe distances and excess pressure at shock air impact of technological explosions on the Magnezitovaya mine personnel was made. The calculation was made for the 15.5 m mine working section, with two conditions of the total section of the mine workings adjacent to the face of 15.5 m and 31 m with distances of 50 m and 100 m. Overpressure was also calculated for a total cross-section of 15.5 m and distances of 150 and 200 m. It was determined that the safe distance for people under overpressure conditions at the shock air wave front, depending on breaking schemes, is in the range of 150-200 m. The urgency of this research is to ensure industrial safety of underground mining operations.
Circulating blood platelets contain small numbers of fully functional mitochondria. Accumulating evidence demonstrates that these mitochondria regulate the pro-thrombotic function of platelets ...through not only energy generation, but also redox signalling and the initiation of apoptosis. Beyond its regulation of haemostasis, platelet mitochondrial function has also traditionally been used to identify and study mitochondrial dysfunction in human disease, owing to the easy accessibility of platelets compared with other metabolically active tissues. In the present article, we provide a brief overview of what is currently known about the function of mitochondria in platelets and review how platelet mitochondria have been used to study mitochondrial function in human disease.
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