scholarly journals Reduced Proteasome Activity and Enhanced Autophagy in Blood Cells of Psoriatic Patients

2020 ◽  
Vol 21 (20) ◽  
pp. 7608 ◽  
Author(s):  
Piotr Karabowicz ◽  
Adam Wroński ◽  
Halina Ostrowska ◽  
Georg Waeg ◽  
Neven Zarkovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Cells ◽  
Protein Adducts ◽  
Akt Pathway ◽  
20S Proteasome ◽  
Carbonyl Groups ◽  
Autophagy Flux ◽  
Cell Components ◽  
Oxidatively Modified ◽  
The Relationship

Psoriasis is a skin disease that is accompanied by oxidative stress resulting in modification of cell components, including proteins. Therefore, we investigated the relationship between the intensity of oxidative stress and the expression and activity of the proteasomal system as well as autophagy, responsible for the degradation of oxidatively modified proteins in the blood cells of patients with psoriasis. Our results showed that the caspase-like, trypsin-like, and chymotrypsin-like activity of the 20S proteasome in lymphocytes, erythrocytes, and granulocytes was lower, while the expression of constitutive proteasome and immunoproteasome subunits in lymphocytes was increased cells of psoriatic patients compared to healthy subjects. Conversely, the expression of constitutive subunits in erythrocytes, and both constitutive and immunoproteasomal subunits in granulocytes were reduced. However, a significant increase in the autophagy flux (assessed using LC3BII/LC3BI ratio) independent of the AKT pathway was observed. The levels of 4-HNE, 4-HNE-protein adducts, and proteins carbonyl groups were significantly higher in the blood cells of psoriatic patients. The decreased activity of the 20S proteasome together with the increased autophagy and the significantly increased level of proteins carbonyl groups and 4-HNE-protein adducts indicate a proteostatic imbalance in the blood cells of patients with psoriasis.

scholarly journals Apelin Promotes ECM Synthesis by Enhancing Autophagy Flux via TFEB in Human Degenerative NP Cells under Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Wei Jiang ◽  
Pei Zhao ◽  
Xuemei Zhang
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Underlying Mechanism ◽  
Autophagic Flux ◽  
Rt Pcr ◽  
Autophagy Flux ◽  
Protein Expressions ◽  
Collagen Ii ◽  
The Relationship ◽  
And Oxidative Stress

Background. Apelin alleviates oxidative stress which contributes to the development of aging. IVDD is a disease closely correlated to aging and oxidative stress which is known to be harmful to NP cells’ matrix synthesis. The purpose of the present study was to investigate the role and underlying mechanism of Apelin in NP cells’ matrix degradation under oxidative stress. Methods. First, the mRNA and protein expressions of Apelin were checked by RT-PCR and Western blot in NP from normal and degenerative IVD to explore the relationship between Apelin and IVDD preliminarily. Then, H2O2 was used to mimic oxidative stress of NP cells. After treated with Apelin 13 and CQ, the GAG content was assessed by DMMB and the mRNA/protein expressions of NP matrix macromolecules (Collagen II and Aggrecan) and autophagy-related markers (LC3 and p62) were assessed by RT-PCR/Western blot. Finally, TFEB was knocked down by esiRNA-TFEB transfection and the nucleoprotein expression of TFEB and autophagy-related markers (LC3 and p62) were assessed by Western blot to discuss whether TFEB is involved in Apelin regulating autophagy flux in NP cells under oxidative stress. Results. Our data first confirmed that the mRNA and protein expressions of Apelin were decreased with IVDD. Furthermore, Apelin increased GAG content of NP cells and mRNA/protein expressions of NP matrix macromolecules (Collagen II and Aggrecan) and promoted autophagic flux (LC3II/I increased and p62 decreased) under oxidative stress. Finally, after transfected with esiRNA-TFEB, Apelin cannot promote autophagic flux any more in human degenerative NP cells. Conclusion. Our data indicated that Apelin promotes ECM synthesis by enhancing autophagy flux via TFEB in human degenerative NP cells under oxidative stress. This viewpoint may provide a new therapeutic idea for IVDD.

scholarly journals Vesiculation red blood cells. Its role in donor erythrocytes components

2020 ◽  
Vol 22 (1) ◽  
pp. 173-179
Author(s):  
V I Vaschenko ◽  
V N Vilyaninov ◽  
L A Skripaj ◽  
E F Sorokoletova
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Structural Changes ◽  
Dehydrogenase Deficiency ◽  
Blood Components ◽  
Band 3 Protein ◽  
Intercellular Interactions ◽  
Cell Components ◽  
Membrane Components ◽  
The Relationship

The formation of microvesicles by blood cells: monocytes, platelets, granulocytes, erythrocytes and endothelial cells is the most important feature of intercellular interactions. Red blood cells form microvesicles to remove damaged cell components, such as oxidized hemoglobin and damaged membrane components, and thus extend their functioning. Two hypotheses have been put forward for the formation of microvesicles: programmed cell death (eryptosis) and clustering of the band 3 protein as a result of disruption of intercellular interactions. In the process of eryptosis, damage to hemoglobin and a change in the pathways of phosphorylation of membrane proteins, primarily protein of strip 3, weaken the strong bonds between the lipid bilayer and the cytoskeleton, which is accompanied by the transformation of the membrane, the formation of protrusions and their transformation into microvesicles. It was found that the formation of microvesicles by red blood cells is impaired in patients suffering from various pathologies of red blood cells: sickle cell anemia, glucose-6-dehydrogenase deficiency, spherocytosis, and malaria. Studies of the last decade show that a violation of the interaction between the membrane and the cytoskeleton is probably the main mechanism, since it is confirmed by data obtained in the study of structural changes in red blood cells of donor hemocomponents stored in a blood bank. Currently, studies on the effect of microvesicles on the safety of erythrocyte-containing blood components have become widespread. A discussion was resumed on the relationship between the number of accumulated microvesicles in blood components and the effectiveness of donor components for patients during transfusion, depending on the shelf life of the components. Detailed data on proteomic, lipidomic and immunogenic comparisons of microvesicles obtained from various sources are convincing in the identification of trigger stimuli causing the generation of microvesicles. Elucidation of the contribution of microvesicles obtained from red blood cells to inflammation, thrombosis, and autoimmune reactions confirms the need to further study the mechanisms and consequences of the generation of microvesicles by red blood cells of donor components used for transfusion medicine.

The importance and significance of gene polymorphisms in preeclampsia

2016 ◽  
pp. 45-49
Author(s):  
P.N. Veropotvelyan ◽  
◽  
I.S. Tsehmistrenko ◽  
N.P. Veropotvelyan ◽  
N.S. Rusak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Early Diagnosis ◽  
Gene Polymorphisms ◽  
Individual Risk ◽  
Extended Study ◽  
Stress Genes ◽  
Detoxification System ◽  
The Individual ◽  
The Relationship

Was to conduct a systematic review of data on the relationship between polymorphisms genes of detoxification system and development of preeclampsia (РЕ). Рresents the main genes of detoxification system (GSTPI, GSTМI, GSTТI, GРХI, ЕРНХI, SOD-2, SOD-3, CYPIAL, MTHЕR, MTR) and their functions. Of interest is the possibility of calculating the individual risk of PE based on the results about the presence of a combination of different polymorphisms in the genotype of the female. Question about early diagnosis of РЕ remains controversial and not fully understood. It is necessary to conduct further in-depth, extended study of this problem. Key words: preeclampsia, oxidative stress, genes of the detoxification system.

Oxidative Stress Levels, JAK2V617F Mutational Status and Thrombotic Complications in Patients with Essential Thrombocythemia

2019 ◽  
Vol 70 (8) ◽  
pp. 2822-2825 ◽  
Author(s):  
Cornel Moisa ◽  
Mihnea Alexandru Gaman ◽  
Camelia Cristina Diaconu ◽  
Amelia Maria Gaman
Keyword(s):  
Oxidative Stress ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasm ◽  
Oxygen Species ◽  
Mutational Status ◽  
Increased Risk ◽  
Stress Levels ◽  
Total Antioxidant ◽  
Thrombotic Complications ◽  
The Relationship

Essential thrombocythemia (ET) is a BCR-ABL1-negative myeloproliferative neoplasm associated with thrombotic and haemorrhagic complications. Reactive oxygen species (ROS) overexpression induces a growth advantage to JAK2V617F-positive clones and, in association with a higher number of immature platelets, leukocytosis, and additional cardiovascular risk factors, leads to an increased risk for thrombotic events. We evaluated oxidative stress by measuring ROS levels and the total antioxidant capacity (TAC) in 62 ET patients and investigated the relationship between oxidative stress, JAK2V617F mutational status and the development of thrombotic events. We found higher oxidative stress levels in JAK2V617F-positive vs. JAK2V617F-negative ET cases with no significant differences between homozygous and heterozygous genotypes. Increased ROS levels and thrombotic events were more frequent in ET patients with old age at diagnosis, higher haematocrit levels or leukocytosis.

Biologically Important Physicochemical Properties of Some Cephalosporins

1992 ◽  
Vol 57 (8) ◽  
pp. 1739-1746
Author(s):  
Katarína Škvareninová ◽  
Štefan Baláž ◽  
Ernest Šturdík ◽  
Miroslav Veverka ◽  
Jana Adamcová ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Partition Coefficients ◽  
Dissociation Constants ◽  
Transport Rate ◽  
Hydrolysis Rate ◽  
Antibacterial Effects ◽  
Oh Groups ◽  
Non Linear Equation ◽  
Cell Components ◽  
The Relationship

In the series of cephalosporin derivatives, consisting of eight 7-(R1-CH2-CO-NH)cephalosporanic acids and of seven analogical compounds with 3-acetoxymethyl replaced by 3-CH3, physicochemical properties, which are expected to play a role in their antibacterial effects (the transport rate parameters and partition coefficients in the systems 1-octanol-water and 1-octanol-buffer, dissociation constants of the 4-carboxyl group, reactivity towards L-glutathione imitating the nucleophilic groups of the cell components and hydrolysis rate parameters), were determined. Linear dependences were observed between the partition coefficients and the π-constants of the varying substituents as well as between reactivity towards SH-groups of L-glutathione and OH-groups. The relationship between the transport rate parameters and partition coefficients, both measured in buffered as well as non-buffered system, was described by a common non-linear equation.

Short-term Effects of Metformin on Cardiac and Peripheral Blood Cells Following Cecal Ligation and Puncture-induced Sepsis

Drug Research ◽  
2020 ◽  
Author(s):  
Tina Didari ◽  
Shokoufeh Hassani ◽  
Maryam Baeeri ◽  
Mona Navaei-Nigjeh ◽  
Mahban Rahimifard ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Weight Loss ◽  
Blood Cells ◽  
Cell Injury ◽  
Antioxidant Properties ◽  
Cecal Ligation ◽  
Neutrophil Infiltration ◽  
Cardiac Cells ◽  
Cecal Ligation And Puncture ◽  
Blood Profile

Abstract Aim of the study Sepsis has well-documented inflammatory effects on cardiovascular and blood cells. This study is designed to investigate potential anti-inflammatory effects of metformin on cardiac and blood cells 12 and 24 h following cecal ligation and puncture (CLP)-induced sepsis. Methods For the purpose of this study, 36 male Wistar rats were divided into six groups: two groups underwent CLP, two groups underwent CLP and received metformin, and two groups only received sham operations. 12 h later, 18 rats (half of rats in each of the three aforementioned groups) were sacrificed and cardiac and blood cells were harvested. Subsequently, 12 h later, the rest of the rats were euthanatized. In all harvested blood and cardiac cells, oxidative stress indicators, antioxidant properties, count of blood cells, neutrophil infiltration, percentage of weight loss and pathological assessment were conducted. Results In our experiment, metformin elevated antioxidant levels, improved function of blood cells and percentage of weight loss. Moreover, in the groups which received metformin, oxidative stress and neutrophil infiltration markers were decreased significantly. Moreover, pathological investigations of cardiac cell injury were reduced in the metformin group. Conclusions Our findings suggest that in CLP induced sepsis model, metformin can improve the function of blood and cardiac cells through alleviating inflammation, improvement of anti-inflammation properties, and enhancement of blood profile, and all these effects are more pronounced after 24 h in comparison with 12 h after induction of sepsis.

scholarly journals Uric Acid, Oxidative Stress and Inflammation in Chronic Heart Failure with Reduced Ejection Fraction

2015 ◽  
Vol 23 (4) ◽  
pp. 397-406 ◽  
Author(s):  
Adriana Iliesiu ◽  
Alexandru Campeanu ◽  
Daciana Marta ◽  
Irina Parvu ◽  
Gabriela Gheorghe
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Uric Acid ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Xanthine Oxidase ◽  
Left Ventricular ◽  
Paraoxonase 1 ◽  
Lv Function ◽  
The Relationship

Abstract Background. Oxidative stress (OS) and inflammation are major mechanisms involved in the progression of chronic heart failure (CHF). Serum uric acid (sUA) is related to CHF severity and could represent a marker of xanthine-oxidase activation. The relationship between sUA, oxidative stress (OS) and inflammation markers was assessed in patients with moderate-severe CHF and reduced left ventricular (LV) ejection fraction (EF). Methods. In 57 patients with stable CHF, functional NYHA class III, with EF<40%, the LV function was assessed by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels and echocardiographically through the EF and E/e’ ratio, a marker of LV filling pressures. The relationship between LV function, sUA, malondialdehyde (MDA), myeloperoxidase (MPO), paraoxonase 1 (PON-1) as OS markers and high sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) as markers of systemic inflammation was evaluated. Results. The mean sUA level was 7.9 ± 2.2 mg/dl, and 61% of the CHF patients had hyperuricemia. CHF patients with elevated LV filling pressures (E/e’ ≥ 13) had higher sUA (8.6 ± 2.3 vs. 7.3 ± 1.4, p=0.08) and NT-proBNP levels (643±430 vs. 2531±709, p=0.003) and lower EF (29.8 ± 3.9 % vs. 36.3 ± 4.4 %, p=0.001). There was a significant correlation between sUA and IL-6 (r = 0.56, p<0.001), MDA (r= 0.49, p= 0.001), MPO (r=0.34, p=0.001) and PON-1 levels (r= −0.39, p= 0.003). Conclusion. In CHF, hyperuricemia is associated with disease severity. High sUA levels in CHF with normal renal function may reflect increased xanthine-oxidase activity linked with chronic inflammatory response.

Binding of aflatoxins to the 20S proteasome: effects on enzyme functionality and implications for oxidative stress and apoptosis

2007 ◽  
Vol 388 (1) ◽  
Author(s):  
Manila Amici ◽  
Valentina Cecarini ◽  
Assuntina Pettinari ◽  
Laura Bonfili ◽  
Mauro Angeletti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
20S Proteasome ◽  
Enzyme Functionality

scholarly journals Regulation of intracellular glutathione levels in erythrocytes infected with chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum

2002 ◽  
Vol 368 (3) ◽  
pp. 761-768 ◽  
Author(s):  
Svenja MEIERJOHANN ◽  
Rolf D. WALTER ◽  
Sylke MÜLLER
Keyword(s):  
Oxidative Stress ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Differential Susceptibility ◽  
Protozoan Parasite ◽  
Chloroquine Resistance ◽  
Glutathione Metabolism ◽  
Glutathione Synthesis ◽  
Intracellular Glutathione ◽  
Glutamylcysteine Synthetase

Malaria is one of the most devastating tropical diseases despite the availability of numerous drugs acting against the protozoan parasite Plasmodium in its human host. However, the development of drug resistance renders most of the existing drugs useless. In the malaria parasite the tripeptide glutathione is not only involved in maintaining an adequate intracellular redox environment and protecting the cell against oxidative stress, but it has also been shown that it degrades non-polymerized ferriprotoporphyrin IX (FP IX) and is thus implicated in the development of chloroquine resistance. Glutathione levels in Plasmodium-infected red blood cells are regulated by glutathione synthesis, glutathione reduction and glutathione efflux. Therefore the effects of drugs that interfere with these metabolic processes were studied to establish possible differences in the regulation of the glutathione metabolism of a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodiumfalciparum. Growth inhibition of P. falciparum 3D7 by d,l-buthionine-(S,R)sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase (γ-GCS), and by Methylene Blue (MB), an inhibitor of gluta thione reductase (GR), was significantly more pronounced than inhibition of P.falciparum Dd2 growth by these drugs. These results correlate with the higher levels of total glutathione in P. falciparum Dd2. Short-term incubations of Percoll-enriched trophozoite-infected red blood cells in the presence of BSO, MB and N,N1-bis(2-chloroethyl)-N-nitrosourea and subsequent determinations of γ-GCS activities, GR activities and glutathione disulphide efflux revealed that maintenance of intracellular glutathione in P. falciparum Dd2 is mainly dependent on glutathione synthesis whereas in P. falciparum 3D7 it is regulated via GR. Generally, P. falciparum Dd2 appears to be able to sustain its intracellular glutathione more efficiently than P. falciparum 3D7. In agreement with these findings is the differential susceptibility to oxidative stress of both parasite strains elicited by the glucose/glucose oxidase system.

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