The role of mitochondria in Ca2+ homeostasis is controversial. We employed the Ca2+-sensitive dye rhod 2 with novel, high temporal and spatial resolution imaging to evaluate changes in the matrix free Ca2+ concentration of individual mitochondria ([Ca2+]m) in agonist-stimulated, primary cultured aortic myocytes. Stimulation with 10 μM serotonin (5-HT) evoked modest cytosolic Ca2+ transients [cytosolic free Ca2+ concentration ([Ca2+]cyt) <500 nM; measured with fura 2] and triggered contractions in short-term cultured myocytes. However, 5-HT triggered a large mitochondrial rhod 2 signal (indicating pronounced elevation of [Ca2+]m) in only 4% of cells. This revealed heterogeneity in the responses of individual mitochondria, all of which stained with MitoTracker Green FM. In contrast, stimulation with 100 μM ATP evoked large cytosolic Ca2+ transients (>1,000 nM) and induced pronounced, reversible elevation of [Ca2+]m(measured as rhod 2 fluorescence) in 60% of cells. This mitochondrial Ca2+ uptake usually lagged behind the cytosolic Ca2+ transient peak by 3–5 s, and [Ca2+]mdeclined more slowly than did bulk [Ca2+]cyt. The uptake delay may prevent mitochondria from interfering with rapid signaling events while enhancing the mitochondrial response to large, long-duration elevations of [Ca2+]cyt. The responses of arterial myocytes to modest physiological stimulation do not, however, depend on such marked changes in [Ca2+]m.
An innovative platform for targeted oral drug delivery is proposed based on the functionalization of drug/dye‐loaded mesoporous silica nanoparticles (MSNs) with a biodegradable nutraceutical (β‐lactoglobulin). The attachment of the nutraceutical not only protects the drug/dye from leaching in acidic environment, but also effectively allows their release in desired basic sites (pH 7.4).
An innovative platform for targeted oral drug delivery is proposed based on the functionalization of drug/dye‐loaded mesoporous silica nanoparticles (MSNs) with a biodegradable nutraceutical (β‐lactoglobulin). The attachment of the nutraceutical not only protects the drug/dye from leaching in acidic environment, but also effectively allows their release in desired basic sites (pH 7.4).
The assessment of human cancer cell proliferation is a common approach in identifying plant extracts that have potential bioactive effects. In this study, we tested the hypothesis that methanolic extracts of peel and flesh from three archetypal mango cultivars, Irwin (IW), Nam Doc Mai (NDM), and Kensington Pride (KP), differentially affect proliferation, extracellular signal-regulated kinase (ERK) activity, and intracellular calcium ([Ca2+]I) signalling in MCF-7 human breast cancer cells. Mango flesh extracts from all three cultivars did not inhibit cell growth, and of the peel extracts only NDM reduced MCF-7 cell proliferation. Mango cultivar peel and flesh extracts did not significantly change ERK phosphorylation compared to controls; however, some reduced relative maximal peak[Ca2+]Iafter adenosine triphosphate stimulation, with NDM peel extract having the greatest effect among the treatments. Our results identify mango interfruit and intrafruit (peel and flesh) extract variability in antiproliferative effects and[Ca2+]Isignalling in MCF-7 breast cancer cells and highlight that parts of the fruit (such as peel and flesh) and cultivar differences are important factors to consider when assessing potential chemopreventive bioactive compounds in plants extracts.
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