1,721,212 research outputs found
Effect of oxidative stress and 3-hydroxytyrosol on DNA methylation levels of miR-9 promoters
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Hydroxytyrosol prevents chondrocyte death under oxidative stress by inducing autophagy through sirtuin 1-dependent and -independent mechanisms
Full text linkBackground Hydroxytyrosol (HT), a major phenolic antioxidant found in olive oil, can afford protection from oxidative stress in several types of non-tumoral cells, including chondrocytes. Autophagy was recently identified as a protective process during osteoarthritis (OA) development and critical for survival of chondrocytes. Therefore we have investigated the possibility to modulate chondrocyte autophagy by HT treatment. Methods DNA damage and cell death were estimated in human C-28/I2 and primary OA chondrocytes exposed to hydrogen peroxide. Autophagic flux and mitophagy were monitored by measuring levels and location of autophagy markers through western blot, immunostaining and confocal laser microscopy. Late autophagic vacuoles were stained with monodansylcadaverine. The involvement of sirtuin 1 (SIRT-1) was evaluated by immunohistochemistry, western blot and gene silencing with specific siRNA. Results HT increases markers of autophagy and protects chondrocytes from DNA damage and cell death induced by oxidative stress. The protective effect requires the deacetylase SIRT-1, which accumulated in the nucleus following HT treatment. In fact silencing of this enzyme prevented HT from promoting the autophagic process and cell survival. Furthermore HT supports autophagy even in a SIRT-1-independent manner, by increasing p62 transcription, required for autophagic degradation of polyubiquitin-containing bodies. Conclusions These results support the potential of HT as a chondroprotective nutraceutical compound against OA, not merely for its antioxidant ability, but as an autophagy and SIRT-1 inducer as well. General significance HT may exert a cytoprotective action by promoting autophagy in cell types that may be damaged in degenerative diseases by oxidative and other stress stimuli
Emerging nutraceuticals in the management of osteoarthritis: focus on 3-hydroxytyrosol in epigenetics and autophagy pathway
Full text linkmTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management
Full text linkCells adapt their metabolism and activities in response to signals from their surroundings, and this ability is essential for their survival in the face of environmental changes. In mammalian tissues a deficit of these mechanisms is commonly associated with cellular aging and degenerative diseases related to aging, such as cardiovascular disease, cancer, immune system decline, and neurological pathologies. Several proteins have been identified as able to respond directly to energy, nutrient, and growth factor levels and stress stimuli in order to mediate adaptations in the cell. Many of these proteins are enzymes that positively or negatively modulate the autophagic process. This review focuses on biochemical mechanisms involving enzymes-specifically, mTOR, AMPK, and Sirt1-that are currently considered important for these adaptive responses, providing an overview of the interactions of the main players in this process
Modulation of Fatty Acid-Related Genes in the Response of H9c2 Cardiac Cells to Palmitate and n-3 Polyunsaturated Fatty Acids
Full text linkWhile high levels of saturated fatty acids are associated with impairment of cardiovascular functions, n-3 polyunsaturated fatty acids (PUFAs) have been shown to exert protective effects. However the molecular mechanisms underlying this evidence are not completely understood. In the present study we have used rat H9c2 ventricular cardiomyoblasts as a cellular model of lipotoxicity to highlight the effects of palmitate, a saturated fatty acid, on genetic and epigenetic modulation of fatty acid metabolism and fate, and the ability of PUFAs, eicosapentaenoic acid, and docosahexaenoic acid, to contrast the actions that may contribute to cardiac dysfunction and remodeling. Treatment with a high dose of palmitate provoked mitochondrial depolarization, apoptosis, and hypertrophy of cardiomyoblasts. Palmitate also enhanced the mRNA levels of sterol regulatory element-binding proteins (SREBPs), a family of master transcription factors for lipogenesis, and it favored the expression of genes encoding key enzymes that metabolically activate palmitate and commit it to biosynthetic pathways. Moreover, miR-33a, a highly conserved microRNA embedded in an intronic sequence of the SREBP2 gene, was co-expressed with the SREBP2 messenger, while its target carnitine palmitoyltransferase-1b was down-regulated. Manipulation of the levels of miR-33a and SREBPs allowed us to understand their involvement in cell death and hypertrophy. The simultaneous addition of PUFAs prevented the effects of palmitate and protected H9c2 cells. These results may have implications for the control of cardiac metabolism and dysfunction, particularly in relation to dietary habits and the quality of fatty acid intake
Polyamine depletion inhibits both the death receptor pathway and the mitochondrial pathway of apoptosis in chondrocytes
No full textTOMATO SEED PRIMING WITH WATER-SOLUBLE POLYSACCHARIDES FROM JANIA ADHAERENS PROMOTES PLANT GROWTH AND INCREASES PLANT RESISTANCE TO SOILBORNE PATHOGENS
No full textMarine macroalgae are a source of natural bioactive compounds, such as polysaccharides, that deserve exploitation in the field of plant disease management. Moreover, current European regulations require that priority should be given to alternative products than synthetic pesticides. In agriculture, algae have been mostly used for their beneficial properties on plant development. In this study, we showed that tomato seed biopriming with water-soluble polysaccharides (WSPs) from the alga Jania adhaerens protects seedlings and adult plants from the soilborne pathogens Fusarium oxysporum f.sp. lycopersici, Pythium ultimum and Rhizoctonia solani artificially inoculated in a growing substrate.
First, WSPs were characterized by FT-IR spectroscopy and seedling emergence, disease severity, and expression of genes related to phenylpropanoid, chlorogenic acid, SAR and ISR pathways, and chitinase and β-1,3 glucanase activities were investigated after seed priming. WSPs FT-IR spectra showed typical bands assigned to alduronic acids and glycosidic linkage formation in polysaccharides. Depending on the WSPs dose, seed treatment enhanced seedling emergence, reduced disease severity and increased plant growth. Moreover, HQT, HCT, PAL, PR1 and PR2 genes were significantly upregulated together with β-1,3 glucanase activity. These results show that algal WSPs have the potential for being considered as natural compounds for soilborne pathogens control in sustainable agriculture
Sulforaphane protects human chondrocytes against cell death induced by various stimuli
No full textChondrocyte cell death can contribute to cartilage degeneration in articular diseases, such as osteoarthritis (OA). Sulforaphane (SFN), a natural compound derived from cruciferous aliment, is well known as an anti-carcinogen, but according to recent evidence it also shows cytoprotective effects on a variety of non-tumoral cells. Therefore we have tested the ability of SFN to protect chondrocytes from cell death in vitro. Treatment of growing monolayer cultures of human C-28/I2 chondrocytes with SFN in the low micro-molecular range for a few days, reduced cell growth without affecting cell survival or inducing apoptosis. However it decreased cell death in C-28/I2 chondrocytes exposed to stimuli previously reported to promptly trigger apoptosis, that is, the cytokine tumor necrosis factor-α (TNF) plus cycloheximide (CHX) or the polyamine analogue N(1),N(11)-diethylnorspermine (DENSPM) plus CHX. In particular pre-treatment with SFN reduced effector and initiator caspase activities and the associated activation of JNK kinases. SFN exerted a cytoprotective action even versus H(2)O(2) , which differently from the previous stimuli induced cell death without producing an evident caspase activation. SFN pre-treatment also prevented caspase activation in three-dimensional micromass cultures of OA chondrocytes stimulated with growth-related oncogene α (GROα), a pro-apoptotic chemokine. The suppression of caspase activation in micromasses appeared to be related to the inhibition of p38 MAPK phosphorylation. In conclusion, the present work shows that low micro-molecular SFN concentrations exert pro-survival and anti-apoptotic actions and influence signaling pathways in a variety of experimental conditions employing chondrocyte cell lines and OA chondrocytes treated with a range of death stimuli
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