scholarly journals Transketolase regulates sensitivity to APR-246 in p53-null cells independently of oxidative stress modulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Julia V. Milne ◽  
Bonnie Z. Zhang ◽  
Kenji M. Fujihara ◽  
Swati Dawar ◽  
Wayne A. Phillips ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Targeted Therapy ◽  
P53 Protein ◽  
Pentose Phosphate ◽  
Antioxidant Systems ◽  
Mutant P53 ◽  
Complex Mechanism ◽  
Increased Sensitivity ◽  
The Relationship ◽  
Tumour Suppressor P53

AbstractThe prevalence and dire implications of mutations in the tumour suppressor, p53, highlight its appeal as a chemotherapeutic target. We recently showed that impairing cellular antioxidant systems via inhibition of SLC7A11, a component of the system xc− cystine-glutamate antiporter, enhances sensitivity to mutant-p53 targeted therapy, APR-246. We investigated whether this synergy extends to other genes, such as those encoding enzymes of the pentose phosphate pathway (PPP). TKT, one of the major enzymes of the PPP, is allegedly regulated by NRF2, which is in turn impaired by accumulated mutant-p53 protein. Therefore, we investigated the relationship between mutant-p53, TKT and sensitivity to APR-246. We found that mutant-p53 does not alter expression of TKT, nor is TKT modulated directly by NRF2, suggesting a more complex mechanism at play. Furthermore, we found that in p53null cells, knockdown of TKT increased sensitivity to APR-246, whilst TKT overexpression conferred resistance to the drug. However, neither permutation elicited any effect on cells overexpressing mutant-p53 protein, despite mediating oxidative stress levels in a similar fashion to that in p53-null cells. In sum, this study has unveiled TKT expression as a determinant for sensitivity to APR-246 in p53-null cells.

scholarly journals The Relationship between Seminal Fluid Hyperviscosity and Oxidative Stress: A Systematic Review

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 356
Author(s):  
Federica Barbagallo ◽  
Sandro La Vignera ◽  
Rossella Cannarella ◽  
Andrea Crafa ◽  
Aldo E. Calogero ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Seminal Fluid ◽  
Antioxidant Systems ◽  
Fluid Viscosity ◽  
The Relationship ◽  
And Oxidative Stress ◽  
Infertile Patients ◽  
Careful Assessment ◽  
Key Parameter

Introduction: Seminal fluid viscosity is a key parameter to achieve fertilization. Viscosity is more frequently increased in patients with infertility. However, the mechanism by which hyperviscosity causes infertility is still poorly understood. As an increased blood viscosity is associated with diseases caused by oxidative stress, it can be supposed that there is a relationship between seminal fluid viscosity and oxidative stress in male infertility. Therefore, this systematic review aims to investigate the relationship between hyperviscous seminal fluid and oxidative stress. Materials and methods: We performed a systematic search on the following databases Pubmed, MEDLINE, Cochrane, and Scopus from the earliest available date to 10 January 2021, using Medical Subjects Headings (MeSH) indexes and keywords searches. The study included all the articles that evaluated the relationship between increased seminal fluid viscosity and oxidative stress. Article reviews even though dealing with seminal fluid hyperviscosity were excluded. Results: 5 articles were included in this systematic review. The results demonstrated an important impairment of antioxidant systems and increased oxidative stress in patients with high seminal fluid viscosity. Conclusions: These findings suggest that a careful assessment of oxidative stress in patients with hyperviscosity may be very useful in clinical practice. Infertile patients with seminal fluid hyperviscosity could benefit from the treatment with antioxidants to protect sperm cells from oxidative damage and to improve their functional properties.

scholarly journals Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 510
Author(s):  
Giuseppina Barrera ◽  
Marie Angele Cucci ◽  
Margherita Grattarola ◽  
Chiara Dianzani ◽  
Giuliana Muzio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Targeted Therapy ◽  
Cancer Cells ◽  
Antioxidant Response ◽  
Redox Status ◽  
Antioxidant Systems ◽  
Drug Induced ◽  
Transcriptional Coactivators ◽  
Metabolic Remodeling

Chemoresistance represents the main obstacle to cancer treatment with both conventional and targeted therapy. Beyond specific molecular alterations, which can lead to targeted therapy, metabolic remodeling, including the control of redox status, plays an important role in cancer cell survival following therapy. Although cancer cells generally have a high basal reactive oxygen species (ROS) level, which makes them more susceptible than normal cells to a further increase of ROS, chemoresistant cancer cells become highly adapted to intrinsic or drug-induced oxidative stress by upregulating their antioxidant systems. The antioxidant response is principally mediated by the transcription factor Nrf2, which has been considered the master regulator of antioxidant and cytoprotective genes. Nrf2 expression is often increased in several types of chemoresistant cancer cells, and its expression is mediated by diverse mechanisms. In addition to Nrf2, other transcription factors and transcriptional coactivators can participate to maintain the high antioxidant levels in chemo and radio-resistant cancer cells. The control of expression and function of these molecules has been recently deepened to identify which of these could be used as a new therapeutic target in the treatment of tumors resistant to conventional therapy. In this review, we report the more recent advances in the study of Nrf2 regulation in chemoresistant cancers and the role played by other transcription factors and transcriptional coactivators in the control of antioxidant responses in chemoresistant cancer cells.

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.

scholarly journals Systematic Identification of Regulators of Oxidative Stress Reveals Non-canonical Roles for Peroxisomal Import and the Pentose Phosphate Pathway

Cell Reports ◽  
2020 ◽  
Vol 30 (5) ◽  
pp. 1417-1433.e7 ◽  
Author(s):  
Michael M. Dubreuil ◽  
David W. Morgens ◽  
Kanji Okumoto ◽  
Masanori Honsho ◽  
Kévin Contrepois ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate ◽  
Systematic Identification

scholarly journals Comparison of coenzyme Q10 or fish oil for prevention of intermittent hypoxia-induced oxidative injury in neonatal rat lungs

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christina D’Agrosa ◽  
Charles L. Cai ◽  
Faisal Siddiqui ◽  
Karen Deslouches ◽  
Stephen Wadowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Lung Injury ◽  
Fish Oil ◽  
Coenzyme Q10 ◽  
Intermittent Hypoxia ◽  
Oxidative Injury ◽  
Adverse Outcomes ◽  
Neonatal Rat ◽  
Antioxidant Systems

Abstract Background Neonatal intermittent hypoxia (IH) results in oxidative distress in preterm infants with immature antioxidant systems, contributing to lung injury. Coenzyme Q10 (CoQ10) and fish oil protect against oxidative injury. We tested the hypothesis that CoQ10 is more effective than fish oil for prevention of IH-induced lung injury in neonatal rats. Methods Newborn rats were exposed to two clinically relevant IH paradigms at birth (P0): (1) 50% O2 with brief hypoxia (12% O2); or (2) room air (RA) with brief hypoxia (12% O2), until P14 during which they were supplemented with daily oral CoQ10, fish oil, or olive oil from P0 to P14. Pups were studied at P14 or placed in RA until P21 with no further treatment. Lungs were assessed for histopathology and morphometry; biomarkers of oxidative stress and lipid peroxidation; and antioxidants. Results Of the two neonatal IH paradigms 21%/12% O2 IH resulted in the most severe outcomes, evidenced by histopathology and morphometry. CoQ10 was effective for preserving lung architecture and reduction of IH-induced oxidative stress biomarkers. In contrast, fish oil resulted in significant adverse outcomes including oversimplified alveoli, hemorrhage, reduced secondary crest formation and thickened septae. This was associated with elevated oxidants and antioxidants activities. Conclusions Data suggest that higher FiO2 may be needed between IH episodes to curtail the damaging effects of IH, and to provide the lungs with necessary respite. The negative outcomes with fish oil supplementation suggest oxidative stress-induced lipid peroxidation.

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