| 1. |
- Bozaykut, Perinur, et al.
(författare)
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HSP70 Inhibition Leads to the Activation of Proteasomal System under Mild Hyperthermia Conditions in Young and Senescent Fibroblasts
- 2020
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Ingår i: Oxidative Medicine and Cellular Longevity. - : Hindawi Publishing Corporation. - 1942-0900 .- 1942-0994. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- Aging has been characterized with the accumulation of oxidized proteins, as a consequence of progressive decline in proteostasis capacity. Among others, proteasomal system is an efficient protein turnover complex to avoid aggregation of oxidized proteins. Heat shock protein 70 (HSP70) is another critical player that is involved in some key processes including the correct folding of misfolded proteins and targeting aggregated proteins to the proteasome for rapid degradation. The aim of this study was to determine the role of proteasomal system and heat shock proteins to maintain proteome balance during replicative senescence in mild hyperthermia conditions. Our results demonstrated that HSP40/70 machinery is induced by mild hyperthermia conditions independent from senescence conditions. Since HSP70 is largely responsible for the rapidly inducible cell protection following hyperthermia, the activation of "heat shock response" resulted in the elevation of HSP40/70 expressions as well as the proteasome activity. Interestingly, when HSP70 expression was inhibited, increased proteasomal activation was shown to be responsive to mild hyperthermia. Since HSP70 is involved in various stress-related pathways such as oxidative and endoplasmic reticulum stress, depletion of HSP70 expression may induce proteasomal degradation to maintain proteome balance of the cell. Thus, our data suggests that in mild heat stress conditions, molecular chaperone HSP70 plays an important role to avoid protein oxidation and aggregation; however, activities of proteasomal system are induced when HSP70 expression is depleted.
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| 2. |
- D. V. Godoy, Paulo R., et al.
(författare)
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Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress
- 2020
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Ingår i: Oxidative Medicine and Cellular Longevity. - : Hindawi Limited. - 1942-0900 .- 1942-0994. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- The presence of glioma stem cells (GSCs), which are enriched in neurospheres, may be connected to the radioresistance of glioblastoma (GBM) due to their enhanced antioxidant defense and elevated DNA repair capacity. The aim was to evaluate the responses to different radiation qualities and to reduce radioresistance of U87MG cells, a GBM cell line. U87MG cells were cultured in a 3D model and irradiated with low (24 mGy/h) and high (0.39 Gy/min) dose rates of low LET gamma and high LET carbon ions (1-2 Gy/min). Thereafter, expression of proteins related to oxidative stress response, extracellular 8-oxo-dG, and neurospheres were determined. LD50 for carbon ions was significantly lower compared to LD50 of high and low dose rate gamma radiation. A significantly higher level of 8-oxo-dG was detected in the media of cells exposed to a low dose rate as compared to a high dose rate of gamma or carbon ions. A downregulation of oxidative stress proteins was also observed (NRF2, hMTH1, and SOD1). The NRF2 gene was knocked down by CRISPR/Cas9 in neurosphere cells, resulting in less self-renewal, more differentiated cells, and less proliferation capacity after irradiation with low and high dose rate gamma rays. Overall, U87MG glioma neurospheres presented differential responses to distinct radiation qualities and NRF2 plays an important role in cellular sensitivity to radiation.
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| 3. |
- Grauers Wiktorin, Hanna, 1990, et al.
(författare)
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NOX2-Derived Reactive Oxygen Species in Cancer.
- 2020
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Ingår i: Oxidative medicine and cellular longevity. - : Hindawi Limited. - 1942-0994 .- 1942-0900. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- The formation of reactive oxygen species (ROS) by the myeloid cell NADPH oxidase NOX2 is critical for the destruction of engulfed microorganisms. However, recent studies imply that ROS, formed by NOX2+ myeloid cells in the malignant microenvironment, exert multiple actions of relevance to the growth and spread of neoplastic cells. By generating ROS, tumor-infiltrating myeloid cells and NOX2+ leukemic myeloid cells may thus (i) compromise the function and viability of adjacent cytotoxic lymphocytes, including natural killer (NK) cells and T cells, (ii) oxidize DNA to trigger cancer-promoting somatic mutations, and (iii) affect the redox balance in cancer cells to control their proliferation and survival. Here, we discuss the impact of NOX2-derived ROS for tumorigenesis, tumor progression, regulation of antitumor immunity, and metastasis. We propose that NOX2 may be a targetable immune checkpoint in cancer.
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| 4. |
- Isaguliants, MG, et al.
(författare)
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Redox Biology of Infection and Consequent Disease
- 2020
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Ingår i: Oxidative medicine and cellular longevity. - : Hindawi Limited. - 1942-0994 .- 1942-0900. ; 2020, s. 5829521-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Mercier, N, et al.
(författare)
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Semicarbazide-Sensitive Amine Oxidase Increases in Calcific Aortic Valve Stenosis and Contributes to Valvular Interstitial Cell Calcification
- 2020
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Ingår i: Oxidative medicine and cellular longevity. - : Hindawi Limited. - 1942-0994 .- 1942-0900. ; 2020, s. 5197376-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Calcific aortic valve stenosis (CAVS) is a common disease associated with aging. Oxidative stress participates in the valve calcification process in CAVS. Semicarbazide-sensitive amine oxidase (SSAO), also referred to as vascular adhesion protein 1 (VAP-1), transforms primary amines into aldehydes, generating hydrogen peroxide and ammonia. SSAO is expressed in calcified aortic valves, but its role in valve calcification has remained largely unexplored. The aims of this study were to characterize the expression and the activity of SSAO during aortic valve calcification and to establish the effects of SSAO inhibition on human valvular interstitial cell (VIC) calcification. Methods. Human aortic valves from n=80 patients were used for mRNA extraction and expression analysis, Western blot, SSAO activity determination, immunohistochemistry, and the isolation of primary VIC cultures. Results. SSAO mRNA, protein, and activity were increased with increasing calcification within human aortic valves and localized in the vicinity of the calcified zones. The valvular SSAO upregulation was consistent after stratification of the subjects according to cardiovascular and CAVS risk factors associated with increased oxidative stress: body mass index, diabetes, and smoking. SSAO mRNA levels were significantly associated with poly(ADP-ribose) polymerase 1 (PARP1) in calcified tissue. Calcification of VIC was inhibited in the presence of the specific SSAO inhibitor LJP1586. Conclusion. The association of SSAO expression and activity with valvular calcification and oxidative stress as well as the decreased VIC calcification by SSAO inhibition points to SSAO as a possible marker and therapeutic target to be further explored in CAVS.
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| 6. |
- Pour Khavari, Ali, et al.
(författare)
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Effects of Tomato Juice Intake on Salivary 8-Oxo-dG Levels as Oxidative Stress Biomarker after Extensive Physical Exercise
- 2020
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Ingår i: Oxidative Medicine and Cellular Longevity. - : Hindawi Limited. - 1942-0900 .- 1942-0994. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- Reactive oxygen species (ROS) at a normal level are important molecules involved in several cellular processes including immune response and cell signalling. Overproduction of ROS may lead to elevated oxidative stress and consequently to age-related diseases. Most of the studies related to oxidative stress in humans have been done on blood samples. However, blood sampling might be painful, requires special qualified personnel, and has to be performed at medical centers. An alternative to blood is saliva. Saliva sampling is noninvasive and can be performed by the donor. Biomarker determination in saliva is becoming an important part of laboratory diagnosis, but method development is needed before it can be used in the clinics. In the present investigation, 16 donors performed extensive physical exercise by cycling and keeping their heart rate at 80% of maximum for 20 minutes. The physical activity was repeated 3 times: before tomato juice intake, after daily intake of 100 ml tomato juice during 3 weeks, and finally 3 weeks after finishing tomato juice intake (washout period). The level of the stress biomarker, salivary 8-oxo-dG, was determined before and after the physical activity. The results indicate that (a) 20 min extensive physical activity increases the level of 8-oxo-dG in saliva significantly (p=0.0078) and (b) daily intake of 100 ml tomato juice may inhibit (p=0.052) overproduction of salivary 8-oxo-dG by 20 min physical activity. We conclude that the 20 min extensive physical activity increases the level of salivary 8-oxo-dG in healthy donors and 100 ml daily intake of tomato juice may inhibit the increase of 8-oxo-dG in saliva.
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| 7. |
- Sinha, Mithun, et al.
(författare)
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Editorial : Redox Homeostasis and Cancer
- 2020
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Ingår i: Oxidative Medicine and Cellular Longevity. - : Hindawi Limited. - 1942-0900 .- 1942-0994. ; 2020
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
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