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Andrew P. Feranchak Matthew A. Lewis Charles Kresge Meghana Sathe Abhijit Bugde Kate Luby-Phelps Peter P. Antich J. Gregory Fitz 《The Journal of biological chemistry》2010,285(11):8138-8147
Extracellular ATP represents an important autocrine/paracrine signaling molecule within the liver. The mechanisms responsible for ATP release are unknown, and alternative pathways have been proposed, including either conductive ATP movement through channels or exocytosis of ATP-enriched vesicles, although direct evidence from liver cells has been lacking. Utilizing dynamic imaging modalities (confocal and total internal reflection fluorescence microscopy and luminescence detection utilizing a high sensitivity CCD camera) at different scales, including confluent cell populations, single cells, and the intracellular submembrane space, we have demonstrated in a model liver cell line that (i) ATP release is not uniform but reflects point source release by a defined subset of cells; (ii) ATP within cells is localized to discrete zones of high intensity that are ∼1 μm in diameter, suggesting a vesicular localization; (iii) these vesicles originate from a bafilomycin A1-sensitive pool, are depleted by hypotonic exposure, and are not rapidly replenished from recycling of endocytic vesicles; and (iv) exocytosis of vesicles in response to cell volume changes depends upon a complex series of signaling events that requires intact microtubules as well as phosphoinositide 3-kinase and protein kinase C. Collectively, these findings are most consistent with an essential role for exocytosis in regulated release of ATP and initiation of purinergic signaling in liver cells. 相似文献
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Tian-Hai Yuan Yi Jiang Xiao-Hong Wang Dian-Long Wang Abhijit Bannerjee Susan Bane James P. Snyder Hai-Xia Lin 《Bioorganic & medicinal chemistry letters》2009,19(4):1148-1151
1-Deoxy-9α-dihydrotaxane analogs 9 and 10 were semi-synthesized from 1-deoxybaccatin VI, isolated from Taxus mairei, and tested for cytotoxic activity. Taxane 9 is 10-fold less cytotoxic than paclitaxel, while 10 is equally active. In the tubulin polymerization assay (ED50 values), 10 is 4-fold less effective than paclitaxel, but 3-fold superior to 9. These observations can be explained by analysis of the corresponding taxane/β-tubulin complexes. 相似文献
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Narayan Chakor Ganesh Patil Diana Writer Giridharan Periyasamy Rajiv Sharma Abhijit Roychowdhury Prabhu Dutt Mishra 《Bioorganic & medicinal chemistry letters》2012,22(21):6608-6610
The first total synthesis of prasinic acid is being reported along with its biological evaluation. The ten step synthesis involved readily available and cheap starting materials and can easily be transposed to large scale manufacturing. The crucial steps of the synthesis included the formation of two different aromatic units (7 and 9) and their coupling reaction. The synthetic prasinic acid exhibited moderate antitumor activity (IC50 4.3–9.1 μM) in different lines of cancer cells. 相似文献
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The objective of this investigation was to evaluate the effect of delivery strategies such as cyclodextrin complexation and
liposomes on the topical delivery of ketorolac acid (KTRA) and ketorolac tromethamine. Ketorolac acid–hydroxypropyl-β-cyclodextrin
solid dispersions (KTRA-CD) were prepared by kneading method. The liposomes containing ketorolac tromethamine (KTRM) and KTRA-CD
were prepared. The in vitro permeation of KTRM solution, KTRA solution, KTRA-CD, and liposomes containing KTRM or KTRA-CD through guinea pig skin was
evaluated. The anti-inflammatory activity of the topically applied KTRA-CD gel (containing 1% w/w KTRA) was compared to that of orally delivered KTRM solution. The KTRA-CD demonstrated significantly higher transdermal transport
of ketorolac as compared to all other systems whereas liposomes significantly reduced the transport of ketorolac. The anti-inflammatory
activity of the topically applied KTRA-CD gel was similar to that of the orally administered KTRM. Thus, cyclodextrin complexation
enabled effective transdermal delivery of the ketorolac. 相似文献
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R. Kale 《BMJ (Clinical research ed.)》1994,309(6959):939-942
Doctors and other health professionals in developing countries are missing out on relevant information about health. A lot of the information they need is available in the developed countries, and those who have it are happy to share it with them. But transporting information, like food or medicines, from one part of the world to another is not an easy task nor is it the complete answer to the information drought. It is one thing to ferry books and journals from Europe to Africa and another to make relevant information available to the right person at the right time at an affordable cost. 相似文献
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R. Kale 《BMJ (Clinical research ed.)》1995,310(6989):1254-1256