Search results for " Damage"
showing 10 items of 1139 documents
Progranulin protects against exaggerated axonal injury and astrogliosis following traumatic brain injury
2016
In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn-/- ) 24 h and 5 days after experimental TBI. Grn-/- mice displayed increased perilesional axonal injury even though the overall brain tissue loss and neurological consequences were similar to wild-type mice. Brain inflammation was …
Depletion of regulatory T cells increases T cell brain infiltration, reactive astrogliosis, and interferon-γ gene expression in acute experimental tr…
2019
Abstract Background Traumatic brain injury (TBI) is a major cause of death and disability. T cells were shown to infiltrate the brain during the first days after injury and to exacerbate tissue damage. The objective of this study was to investigate the hitherto unresolved role of immunosuppressive, regulatory T cells (Tregs) in experimental TBI. Methods “Depletion of regulatory T cell” (DEREG) and wild type (WT) C57Bl/6 mice, treated with diphtheria toxin (DTx) to deplete Tregs or to serve as control, were subjected to the controlled cortical impact (CCI) model of TBI. Neurological and motor deficits were examined until 5 days post-injury (dpi). At the 5 dpi endpoint, (immuno-) histological…
Oxidative Stress: A Unifying Mechanism for Cell Damage Induced by Noise, (Water-Pipe) Smoking, and Emotional Stress-Therapeutic Strategies Targeting …
2018
Modern technologies have eased our lives but these conveniences can impact our lifestyles in destructive ways. Noise pollution, mental stresses, and smoking (as a stress-relieving solution) are some environmental hazards that affect our well-being and healthcare budgets. Scrutinizing their pathophysiology could lead to solutions to reduce their harmful effects. Recent Advances: Oxidative stress plays an important role in initiating local and systemic inflammation after noise pollution, mental stress, and smoking. Lipid peroxidation and release of lysolipid by-products, disturbance in activation and function of nuclear factor erythroid 2-related factor 2 (Nrf2), induction of stress hormones …
Activin Receptor Ligand Blocking and Cancer Have Distinct Effects on Protein and Redox Homeostasis in Skeletal Muscle and Liver
2019
Muscle wasting in cancer cachexia can be alleviated by blocking activin receptor type 2 (ACVR2) ligands through changes in protein synthesis/degradation. These changes in cellular and protein metabolism may alter protein homeostasis. First, we elucidated the acute (1–2 days) and 2-week effects of blocking ACVR2 ligands by soluble activin receptor 2B (sACVR2B-Fc) on unfolded protein response (UPR), heat shock proteins (HSPs) and redox balance in a healthy mouse skeletal muscle. Second, we examined UPR, autophagy and redox balance with or without sACVR2B-Fc administration in muscle and liver of C26 tumor-bearing mice. The indicators of UPR and HSPs were not altered 1–2 days after a single sAC…
Effects of air pollution particles (ultrafine and fine particulate matter) on mitochondrial function and oxidative stress – Implications for cardiova…
2020
Environmental pollution is a major cause of global mortality and burden of disease. All chemical pollution forms together may be responsible for up to 12 million annual excess deaths as estimated by the Lancet Commission on pollution and health as well as the World Health Organization. Ambient air pollution by particulate matter (PM) and ozone was found to be associated with an all-cause mortality rate of up to 9 million in the year 2015, with the majority being of cerebro- and cardiovascular nature (e.g. stroke and ischemic heart disease). Recent evidence suggests that exposure to airborne particles and gases contributes to and accelerates neurodegenerative diseases. Especially, airborne t…
Impaired DNA demethylation of C/EBP sites causes premature aging
2018
Changes in DNA methylation are among the best-documented epigenetic alterations accompanying organismal aging. However, whether and how altered DNA methylation is causally involved in aging have remained elusive. GADD45α (growth arrest and DNA damage protein 45A) and ING1 (inhibitor of growth family member 1) are adapter proteins for site-specific demethylation by TET (ten-eleven translocation) methylcytosine dioxygenases. Here we show that Gadd45a/Ing1 double-knockout mice display segmental progeria and phenocopy impaired energy homeostasis and lipodystrophy characteristic of Cebp (CCAAT/enhancer-binding protein) mutants. Correspondingly, GADD45α occupies C/EBPβ/δ-dependent superenhancers …
Mechanisms of beauvericin toxicity and antioxidant cellular defense
2015
Beauvericin (BEA) is a secondary metabolite produced by many species of fungus Fusarium. This study determines the injury (cell viability, cell proliferation, mitochondrial membrane potential, cell death and DNA damage) and the intracellular defense mechanisms (catalase and superoxide dismutase) in Chinese Hamster ovary (CHO-K1) cells after BEA exposure. The results obtained in this study demonstrated that BEA induces cytotoxicity in a dose- and time-dependent manner in CHO-K1 cells. Moreover, disruption in mitochondrial enzymatic activity and cell proliferation has been observed after BEA exposure, which can lead or be consequence of cell death. BEA inhibits cell proliferation by arresting…
Biological activity of PtIV prodrugs triggered by riboflavin-mediated bioorthogonal photocatalysis
2018
AbstractWe have recently demonstrated that riboflavin (Rf) functions as unconventional bioorthogonal photocatalyst for the activation of PtIV prodrugs. In this study, we show how the combination of light and Rf with two PtIV prodrugs is a feasible strategy for light-mediated pancreatic cancer cell death induction. In Capan-1 cells, which have high tolerance against photodynamic therapy, Rf-mediated activation of the cisplatin and carboplatin prodrugs cis,cis,trans-[Pt(NH3)2(Cl)2(O2CCH2CH2CO2H)2] (1) and cis,cis,trans-[Pt(NH3)2(CBDCA)(O2CCH2CH2CO2H)2] (2, where CBDCA = cyclobutane dicarboxylate) resulted in pronounced reduction of the cell viability, including under hypoxia conditions. Such …
Regulation of E2F1 Transcription Factor by Ubiquitin Conjugation
2017
IF 3.226; International audience; Ubiquitination is a post-translational modification that defines the cellular fate of intracellular proteins. It can modify their stability, their activity, their subcellular location, and even their interacting pattern. This modification is a reversible event whose implementation is easy and fast. It contributes to the rapid adaptation of the cells to physiological intracellular variations and to intracellular or environmental stresses. E2F1 (E2 promoter binding factor 1) transcription factor is a potent cell cycle regulator. It displays contradictory functions able to regulate both cell proliferation and cell death. Its expression and activity are tightly…
Suicidal Erythrocyte Death in Metabolic Syndrome.
2021
Eryptosis is a coordinated, programmed cell death culminating with the disposal of cells without disruption of the cell membrane and the release of endocellular oxidative and pro-inflammatory milieu. While providing a convenient form of death for erythrocytes, dysregulated eryptosis may result in a series of detrimental and harmful pathological consequences highly related to the endothelial dysfunction (ED). Metabolic syndrome (MetS) is described as a cluster of cardiometabolic factors (hyperglycemia, dyslipidemia, hypertension and obesity) that increases the risk of cardiovascular complications such as those related to diabetes and atherosclerosis. In the light of the crucial role exerted …