Search results for "Cell biology"

The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor

2021

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various in vitro and in vivo models of neuronal and non-neuronal damage. Although initially characterized as a secreted neurotrophic factor for midbrain dopamine neurons, MANF has recently gained more interest for its intracellular role in regulating the ER homeostasis, including serving as a cofactor of the chaperone glucose-regulated protein 78 (GRP78). We aimed for a better understanding of the neuroprotective mechanisms of MANF. Here we show for the first time that MANF promotes the survival of …

2020

Bilberries (Vaccinium myrtillus L.) have been reported to hold a plentitude of health-promoting properties beyond basic nutrition, mainly attributed to their anthocyanin content and antioxidant activity. In this article, we built the phytochemical profile of three wild bilberry fruit extract formulations (aqueous, methanolic, and hydro-methanolic) using UHPLC-ESI-MS/MS putative analysis, identifying 88 individual phytochemicals, mainly flavonoids (total content 8.41 ± 0.11 mg QE/g dw), free amino acids, polyphenols (total content 21.68 ± 0.19 mg GAE/g dw), carboxylic acids, and vitamins. Furthermore, the antioxidant activity of the extract was assessed, reaching 78.03 ± 0.16% DPPH free radi…

Oxidative stress and antioxidants in the pathophysiology of malignant melanoma.

2018

Abstract The high number of somatic mutations in the melanoma genome associated with cumulative ultra violet (UV) exposure has rendered it one of the most difficult of cancers to treat. With new treatment approaches based on targeted and immune therapies, drug resistance has appeared as a consistent problem. Redox biology, including reactive oxygen and nitrogen species (ROS and RNS), plays a central role in all aspects of melanoma pathophysiology, from initiation to progression and to metastatic cells. The involvement of melanin production and UV radiation in ROS/RNS generation has rendered the melanocytic lineage a unique system for studying redox biology. Overall, an elevated oxidative st…

DNA Methylation and Potential for Epigenetic Regulation in Pygospio elegans.

2015

Transitions in developmental mode are common evolutionarily, but how and why they occur is not understood. Developmental mode describes larval phenotypes, including morphology, ecology and behavior of larvae, which typically are generalized across different species. The polychaete worm Pygospio elegans is one of few species polymorphic in developmental mode, with multiple larval phenotypes, providing a possibility to examine the potential mechanisms allowing transitions in developmental mode. We investigated the presence of DNA methylation in P. elegans, and, since maternal provisioning is a key factor determining eventual larval phenotype, we compared patterns of DNA methylation in females…

Simultaneous lipidomic and transcriptomic profiling in mouse brain punches of acute epileptic seizure model compared to controls

2018

In this study, we report the development of a dual extraction protocol for RNA and lipids, including phospholipids, endocannabinoids, and arachidonic acid, at high spatial resolution, e.g., brain punches obtained from whole frozen brains corresponding to four brain subregions: dorsal hippocampus, ventral hippocampus, basolateral amygdala, and hypothalamus. This extraction method combined with LC/multiple reaction monitoring for lipid quantification and quantitative PCR for RNA investigation allows lipidomic and transcriptomic profiling from submilligram amounts of tissue, thus benefiting the time and animal costs for analysis and the data reliability due to prevention of biological variabil…

Targeting distinct myeloid cell populations in vivo using polymers, liposomes and microbubbles

2016

Identifying intended or accidental cellular targets for drug delivery systems is highly relevant for evaluating therapeutic and toxic effects. However, limited knowledge exists on the distribution of nano- and micrometer-sized carrier systems at the cellular level in different organs. We hypothesized that clinically relevant carrier materials, differing in composition and size, are able to target distinct myeloid cell subsets that control inflammatory processes, such as macrophages, neutrophils, monocytes and dendritic cells. Therefore, we analyzed the biodistribution and in vivo cellular uptake of intravenously injected poly(N-(2-hydroxypropyl) methacrylamide) polymers, PEGylated liposomes…

Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis

2018

Summary Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional respons…

Characterization of a Fetal Liver Cell Population Endowed with Long-Term Multiorgan Endothelial Reconstitution Potential.

2016

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Extracellular vesicles in the oligodendrocyte microenvironment

2019

Abstract Extracellular vesicles (EVs) recently took centre stage as mediators of cellular crosstalk modulating the tissue microenvironment. Released by all types of neural cells, EVs may execute a broad spectrum of functions ranging from maintenance of neuronal homeostasis and regulation of neural plasticity to the spread of neurodegenerative agents. Myelinating oligodendrocytes and axons form a highly specialized functional entity that depends on intimate interactions within the oligodendrocyte-neuron niche. EVs released by oligodendrocytes are internalized by neurons in response to neuronal signals and exhibit neuroprotective properties but also may influence other cells present in the mi…

Double methylation of tRNA-U54 to 2′-O-methylthymidine (Tm) synergistically decreases immune response by Toll-like receptor 7

2018

Abstract Sensing of nucleic acids for molecular discrimination between self and non-self is a challenging task for the innate immune system. RNA acts as a potent stimulus for pattern recognition receptors including in particular human Toll-like receptor 7 (TLR7). Certain RNA modifications limit potentially harmful self-recognition of endogenous RNA. Previous studies had identified the 2′-O-methylation of guanosine 18 (Gm18) within tRNAs as an antagonist of TLR7 leading to an impaired immune response. However, human tRNALys3 was non-stimulatory despite lacking Gm18. To identify the underlying molecular principle, interferon responses of human peripheral blood mononuclear cells to differentia…