scholarly journals Neurotoxic Effects oftrans-Glutaconic Acid in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Patrícia F. Schuck ◽  
Estela N. B. Busanello ◽  
Anelise M. Tonin ◽  
Carolina M. Viegas ◽  
Gustavo C. Ferreira
Keyword(s):  
Chain Complex ◽  
Thiobarbituric Acid ◽  
Glutaric Aciduria Type ◽  
Antioxidant Defenses ◽  
Type I ◽  
Complex Iv ◽  
Spontaneous Chemiluminescence ◽  
Glutaconic Acid ◽  
And Oxidative Stress

trans-Glutaconic acid (tGA) is an unsaturated C5-dicarboxylic acid which may be found accumulated in glutaric aciduria type I, whose pathophysiology is still uncertain. In the present work it was investigated thein vitroeffect of increasingtGA concentrations on neurochemical and oxidative stress parameters in rat cerebral cortex. We observed that Na+, K+-ATPase activity was reduced bytGA, but not creatine kinase, respiratory chain complex IV, and ATP synthase activities. On the other hand,tGA significantly increased lipid peroxidation (thiobarbituric acid-reactive species levels and spontaneous chemiluminescence), as well as protein oxidative damage (oxidation of sulfhydryl groups).tGA also significantly decreased nonenzymatic antioxidant defenses (TRAP and reduced glutathione levels). Our data suggest thattGA may be neurotoxic in rat brain.

scholarly journals Formation of 3-hydroxyglutaric acid in glutaric aciduria type I: in vitro participation of medium chain acyl-CoA dehydrogenase

JIMD Reports ◽  
2019 ◽  
Vol 47 (1) ◽  
pp. 30-34 ◽  
Author(s):  
Verena Peters ◽  
Marina Morath ◽  
Matthias Mack ◽  
Michael Liesert ◽  
Wolfgang Buckel ◽  
...  
Keyword(s):  
Glutaric Aciduria Type ◽  
Type I ◽  
Glutaric Aciduria ◽  
Medium Chain ◽  
Glutaric Aciduria Type I ◽  
Chain Acyl ◽  
Hydroxyglutaric Acid

Glutaric Aciduria Type I

2017 ◽  
Author(s):  
Hilary Vernon
Keyword(s):  
Glutaric Aciduria Type ◽  
Type I ◽  
Glutaric Aciduria ◽  
Glutaric Aciduria Type I ◽  
Intercurrent Illness ◽  
Abnormal Accumulation ◽  
Injury Treatment ◽  
Glutaconic Acid ◽  
Metabolic Management ◽  
Untreated Individuals

Glutaric Aciduria type I is a recessive inborn error of metabolism caused by deficiency of glutaryl-CoA dehydrogenase. This enzyme is responsible for catabolism of L-lysine, L-hydroxylysine, and L-tryptophan. Deficiency of this enzyme leads to abnormal accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine. Untreated individuals are at extremely high risk for encephalopathic crisis, usually triggered by an intercurrent illness or other stressor, and typically occurring between 3 and 36 months of age. This crisis classically results in bilateral striatal injury. Treatment, which can help to prevent encephalopathic crises, includes dietary lysine restriction, carnitine supplementation, and careful metabolic management during intercurrent illness.

scholarly journals Regulation of neutrophil gelatinase-associated lipocalin in aortic valve stenosis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E Jover ◽  
L Matilla ◽  
M Garaikoetxea ◽  
A Fernandez-Celis ◽  
R Sabada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aortic Valve ◽  
Type I ◽  
Serum Samples ◽  
Alizarin Red ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Wide Range ◽  
Neutrophil Gelatinase ◽  
And Oxidative Stress

Abstract Background Aortic valve (AV) stenosis is the commonest form of adult valvular heart disease (VHD) and affects 4.5% of the general population aged over 60 years. Owing to multifactorial and complex molecular events, the valve interstitial cell (VIC) undergoes myofibroblast and osteoblast differentiation. Neutrophil gelatinase-associated lipocalin (NGAL) is a pleiotropic glycoprotein belonging to the lipocalin family and it is expressed in a wide range of tissues and cell types. It is deregulated in several diseases with both detrimental and beneficial effects. NGAL mainly signals towards 24p3R. Purpose We aimed to confirm the expression of NGAL in human AV stenosis and its association with inflammation, oxidative stress, fibrosis/remodeling and calcification, and its regulation in calcifying VICs. Methods Surgical AV leftovers were harvested from patients undergoing elective surgical valve replacement with no kidney disease. Serum samples were collected within the 24h before the surgery. AV were histologically assessed by hematoxylin-eosin, Movat, Alizarin Red and Alcian blue/Sirius Red staining and immunohistochemistry. Western blotting, ELISA and zymography were used in molecular biology studies. VICs were challenged for 2, 4 and 8 days with hyperphosphate (2.6mM, HP) media ± rhNGAL for in vitro validation studies. Results NGAL was quantified in AVs and serum samples from 126 donors (57.4% men). Circulating NGAL was associated with circulating inflammation (Tumor Necrosis Factor-α, Interleukin (IL)-6 and ICAM-1) and oxidative stress (Myeloperoxidase (MPO) and 8OHdG) markers. Likewise, tissue NGAL was correlated with inflammation (IL-6, RANTES and Galectin-3), oxidative stress (MPO, Endothelial Nitric Oxide Synthase, Malondialdehyde (MDA) and Carboxy Methyl Lysine (CML)) and fibrosis (Collagen type I). Osteoblast markers, metalloproteinase (MMP)-9 expression or its activity were not associated with NGAL. NGAL was greater expressed in men than women (217.70±23.41 vs. 119.5±11.31, p=0.0098). In vitro, intracellular NGAL and 24p3R were strongly down-regulated in calcifying men-derived VICs (n=6) whereas secretion of NGAL was enhanced from day 4 (0.55±0.15, p=0.0283; 0.32±0.09 p<0.0001; 8.00±2.32, p=0.0053 fold changes, respectively). This may reflect reduced 24p3R-dependent signalling in osteoblast-like VICs. Such effects were overall negated in women-derived VICs (n=3). RhNGAL endowed calcifying VICs with increased necrosis (52KDa-cPARP1), apoptosis (cCaspase 3) and oxidative stress (CML, MDA, nitrotyrosine and pNF-kB) at day 8. Conclusions NGAL is associated with inflammation, oxidative stress and fibrosis in AV stenosis, and promotes pro-apoptotic and necrotic phenotypes in vitro. Our results suggest that NGAL signaling may drive sex-dependent differences clinically relevant to the VHD pathogenesis. The challenge is now to understand how NGAL signals in men/women-derived VICs. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III

Exercise-induced dehydration with and without environmental heat stress results in increased oxidative stress

2011 ◽  
Vol 36 (5) ◽  
pp. 698-706 ◽  
Author(s):  
Angela R. Hillman ◽  
Rebecca V. Vince ◽  
Lee Taylor ◽  
Lars McNaughton ◽  
Nigel Mitchell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cellular Stress ◽  
Time Trial ◽  
Thiobarbituric Acid ◽  
Hydration Status ◽  
Warm Environment ◽  
Exercise Induced ◽  
And Oxidative Stress

While in vitro work has revealed that dehydration and hyperthermia can elicit increased cellular and oxidative stress, in vivo research linking dehydration, hyperthermia, and oxidative stress is limited. The purpose of this study was to investigate the effects of exercise-induced dehydration with and without hyperthermia on oxidative stress. Seven healthy male, trained cyclists (power output (W) at lactate threshold (LT): 199 ± 19 W) completed 90 min of cycling exercise at 95% LT followed by a 5-km time trial (TT) in 4 trials: (i) euhydration in a warm environment (EU-W, control), (ii) dehydration in a warm environment (DE-W), (iii) euhydration in a thermoneutral environment (EU-T), and (iv) dehydration in a thermoneutral environment (DE-T) (W: 33.9 ± 0.9 °C; T: 23.0 ± 1.0 °C). Oxidized glutathione (GSSG) increased significantly postexercise in dehydration trials only (DE-W: p < 0.01, DE-T: p = 0.03), and while not significant, total glutathione (TGSH) and thiobarbituric acid reactive substances (TBARS) tended to increase postexercise in dehydration trials (p = 0.08 for both). Monocyte heat shock protein 72 (HSP72) concentration was increased (p = 0.01) while lymphocyte HSP32 concentration was decreased for all trials (p = 0.02). Exercise-induced dehydration led to an increase in GSSG concentration while maintenance of euhydration attenuated these increases regardless of environmental condition. Additionally, we found evidence of increased cellular stress (measured via HSP) during all trials independent of hydration status and environment. Finally, both 90-min and 5-km TT performances were reduced during only the DE-W trial, likely a result of combined cellular stress, hyperthermia, and dehydration. These findings highlight the importance of fluid consumption during exercise to attenuate thermal and oxidative stress during prolonged exercise in the heat.

Collagen fibrillogenesis in vitro: interaction of types I and V collagen

1986 ◽  
Vol 44 ◽  
pp. 210-211
Author(s):  
Arthur J. Wasserman ◽  
Kathy C. Kloos ◽  
David E. Birk
Keyword(s):  
Type I Collagen ◽  
Corneal Stroma ◽  
Minor Component ◽  
Homogeneous Distribution ◽  
Type I ◽  
Type V Collagen ◽  
Fibril Morphology ◽  
Type V ◽  
In Vitro Interaction

Type I collagen is the predominant collagen in the cornea with type V collagen being a quantitatively minor component. However, the content of type V collagen (10-20%) in the cornea is high when compared to other tissues containing predominantly type I collagen. The corneal stroma has a homogeneous distribution of these two collagens, however, immunochemical localization of type V collagen requires the disruption of type I collagen structure. This indicates that these collagens may be arranged as heterpolymeric fibrils. This arrangement may be responsible for the control of fibril diameter necessary for corneal transparency. The purpose of this work is to study the in vitro assembly of collagen type V and to determine whether the interactions of these collagens influence fibril morphology.

Use of guidelines improves the neurological outcome in glutaric aciduria type I

2010 ◽  
Vol 41 (02) ◽  
Author(s):  
J Heringer ◽  
SPN Boy ◽  
R Ensenauer ◽  
B Assmann ◽  
J Zschocke ◽  
...  
Keyword(s):  
Neurological Outcome ◽  
Glutaric Aciduria Type ◽  
Type I ◽  
Glutaric Aciduria ◽  
Glutaric Aciduria Type I

Development of Neuropsychological Functions in Patients with Glutaric Aciduria Type I

2014 ◽  
Vol 45 (S 01) ◽  
Author(s):  
N. Boy ◽  
J. Heringer ◽  
G. Haege ◽  
E. Glahn ◽  
G. Hoffmann ◽  
...  
Keyword(s):  
Glutaric Aciduria Type ◽  
Type I ◽  
Glutaric Aciduria ◽  
Glutaric Aciduria Type I ◽  
Neuropsychological Functions

Plasminogen Activation in Diabetes Mellitus: Normalization of Blood Sugar Levels Improves Impaired Enzyme Kinetics In Vitro

1985 ◽  
Vol 54 (02) ◽  
pp. 413-414 ◽  
Author(s):  
Margarethe Geiger ◽  
Bernd R Binder
Keyword(s):  
Plasminogen Activator ◽  
Blood Sugar ◽  
Metabolic Disorders ◽  
Normal Values ◽  
Diabetic Patients ◽  
Type I ◽  
Plasminogen Activation ◽  
Lag Period ◽  
Sugar Levels

SummaryWe have demonstrated previously that fibrin enhanced plasmin formation by the vascular plasminogen activator was significantly impaired, when components isolated from the plasma of three uncontrolled diabetic patients (type I) were used to study plasminogen activation in vitro. In the present study it can be demonstrated that functional properties of the vascular plasminogen activators as well as of the plasminogens from the same three diabetic patients are significantly improved after normalization of blood sugar levels and improvement of HbAlc values. Most pronounced the Km of diabetic vascular plasminogen activator in the presence of fibrin returned to normal values, and for diabetic plasminogen the prolonged lag period until maximal plasmin formation occurred was shortened to almost control values. From these data we conclude that the observed abnormalities of in vitro fibrinolysis are not primarily associated with the diabetic disease, but might be secondary to metabolic disorders caused by diabetes.

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