Search results for "mitochondrial"
showing 10 items of 919 documents
Revisiting the Warburg effect: historical dogma versus current understanding
2020
Contrary to Warburg's original thesis, accelerated aerobic glycolysis is not a primary, permanent and universal consequence of dysfunctional or impaired mitochondria compensating for poor ATP yield per mole of glucose. Instead, in most tumours the Warburg effect is an essential part of a 'selfish' metabolic reprogramming, which results from the interplay between (normoxic/hypoxic) hypoxia-inducible factor-1 (HIF-1) overexpression, oncogene activation (cMyc, Ras), loss of function of tumour suppressors (mutant p53, mutant phosphatase and tensin homologue (PTEN), microRNAs and sirtuins with suppressor functions), activated (PI3K-Akt-mTORC1, Ras-Raf-MEK-ERK-cMyc, Jak-Stat3) or deactivated (LKB…
Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase
2016
Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (…
Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis
2019
Summary While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressi…
Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes
2016
The Bcl-2 (B-cell lymphoma 2) protein Bax (Bcl-2 associated X, apoptosis regulator) can commit cells to apoptosis via outer mitochondrial membrane permeabilization. Bax activity is controlled in healthy cells by prosurvival Bcl-2 proteins. C-terminal Bax transmembrane domain interactions were implicated recently in Bax pore formation. Here, we show that the isolated transmembrane domains of Bax, Bcl-xL (B-cell lymphoma-extra large), and Bcl-2 can mediate interactions between Bax and prosurvival proteins inside the membrane in the absence of apoptotic stimuli. Bcl-2 protein transmembrane domains specifically homooligomerize and heterooligomerize in bacterial and mitochondrial membranes. Thei…
Cytotoxicity of 18 Cameroonian medicinal plants against drug sensitive and multi-factorial drug resistant cancer cells
2018
Abstract Ethnopharmacological relevance Cameroonian medicinal plants are traditionally used to treat many ailments, including cancer and related diseases. Cancer is characterized as a condition with complex signs and symptoms. It has been recommended that ethnopharmacological usages such as immune and skin disorders, inflammatory, infectious, parasitic and viral diseases should be taken into account when selecting plants for anticancer screenings, since these reflect disease states bearing relevance to cancer or cancer-like symptoms. Aim of the study The present study aims at investigating 20 methanol extracts from 15 Cameroonian medicinal plants on a panel of human cancer cell lines, inclu…
Female-specific association among I, J and K mitochondrial genetic haplogroups and cancer:A longitudinal cohort study
2018
Recent studies highlighted the role of mitochondrial dysregulation in cancer, suggesting that the different mitochondrial haplogroups might play a role in tumorigenesis and risk of cancer development. Our aim is to investigate whether any mitochondrial haplogroups carried a significant higher risk of cancer development in a large prospective cohort of North American people. The haplogroup assignment was performed by a combination of sequencing and PCR-RFLP techniques. Our specific outcome of interest was the incidence of any cancer during follow-up period. Overall, 3222 participants were included in the analysis. Women having I, J, K haplogroup reported a significant higher incidence of can…
Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts
2016
The research leading to these results was funded by the Spanish Ministry of Health (FIS-PI11/00610, FIS-PI041436, FIS-PI081151, FIS-PI042018, and FIS-PI09/02311), the European Union (EU) (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), the Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, CP11/00178, FIS-PI06/0867, and FIS-PS09/00090), the Conselleria de Sanitat Generalitat Valenciana, the Generalitat de Catalunya-CIRIT (1999SGR 00241), the Obre Social Cajastur, the Universidad de Oviedo, the Department of Health of the Basque Government (2005111093 and 2009111069),…
Prenatal Air Pollution and Reduced Birth Weight: Decline in Placental Mitochondria as a Potential Mechanism.
2016
Strong epidemiological evidence links prenatal exposure to ambient air pollution and outcomes including low birth weight, intrauterine growth restriction, and preterm birth.1,2 A new study finds evidence that the association between prenatal air pollution exposure and reduced birth weight may be mediated in part by a decline in the mitochondrial content of the placenta.3 During pregnancy, the placenta supports the nourishment, growth, and development of the fetus, and mitochondria within the cells of the placenta are essential to these processes.4 Mitochondria, the cellular organelles that regulate energy production, are easily damaged by reactive oxygen species generated by oxidative stres…
(+)-Pentazocine reduces oxidative stress and apoptosis in microglia following hypoxia/reoxygenation injury
2016
Abstract Background Sigma-1 receptors (σ 1 R) are highly expressed in neurons as well as microglia and have been shown to modulate the inflammatory response in the central nervous system and thus may serve as possible target for neuroprotective strategies. The aim of the present study was to test the effect of (+)-pentazocine, a putative σ 1 R agonist, in an in vitro model of microglia activation. Methods Microglia (BV2 cells) was exposed (3 h) to 1% oxygen and reoxygenation was allowed for 24 h. Cells were treated with different concentrations (1, 10, 25 and 50 μM) of (+)-pentazocine in the presence or absence of NE-100 (1 μM), a well established σ 1 R antagonist. Cell viability and apopto…
Cytotoxicity and mode of action of a naturally occurring naphthoquinone, 2-acetyl-7-methoxynaphtho[2,3-b]furan-4,9-quinone towards multi-factorial dr…
2017
Abstract Introduction Malignacies are still a major public concern worldwide and despite the intensive search of new chemotherapeutic agents, treatment still remains a challenging issue. The present study was designed to evaluate the cytotoxicity of 2-acetyl-7-methoxynaphtho[2,3-b]furan-4,9-quinone (AMNQ) isolated from the bark of Milletia versicolor towards a panel of drug-sensitive and multidrug-resistant (MDR) cancer cell lines. Methods The resazurin reduction assay was used to evaluate the cytotoxicity of AMNQ against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species were all analyze…