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51.
GD3 recruits reactive oxygen species to induce cell proliferation and apoptosis in human aortic smooth muscle cells 总被引:6,自引:0,他引:6
Sialic acid containing glycosphingolipids (gangliosides) are expressed on the surface of all mammalian cells and have been implicated in regulating various biological phenomena; however, the detailed signaling mechanisms involved in this process are not known. We report here a novel aspect of disialoganglioside, GD3-mediated regulation of cell proliferation and cell death via the recruitment of reactive oxygen species (ROS). A low concentration (2.5-10 microm) of GD3, incubated with human aortic smooth muscle cells for a short period of time (10-30 min), stimulates superoxide generation via the activation of both NADPH oxidase and NADH oxidase activity. This leads to downstream signaling leading to cell proliferation and apoptosis. However, [(3)H]GD3 incubated with the cells under such conditions was found in a trypsin-sensitive fraction that was separable from endogenous GD3. The exact mechanism causing ROS generation and downstream signaling remains to be elucidated. The uptake of GD3 was accompanied by a 2.5-fold stimulation in the activity of mitogen-activated protein (MAP) kinase and 5-fold stimulation in cell proliferation. Preincubation of cells with membrane-permeable antioxidants, pyrrolidine dithiocarbamate, and N-acetylcysteine abrogated the superoxide generation and cell proliferation. In contrast, at higher concentrations (50-200 microm) GD3 inhibited the generation of superoxides but markedly stimulated the generation of nitric oxide (NO) (10-fold compared with control). This in turn stimulated mitochondrial cytochrome c release and intrachromosomal DNA fragmentation, which lead to apoptosis. In sum, at a low concentration, GD3 recruits superoxides to activate p44 MAPK and stimulates cell proliferation. In contrast, at high concentrations GD3 recruits nitric oxide to scavenge superoxide radicals that triggered signaling events that led to apoptosis. These observations might have relevance in regard to the potential role of GD3 in aortic smooth muscle cell proliferation and apoptosis that may contribute to plaque rupture in atherosclerosis. 相似文献
52.
Yadav MR Shinde AK Chouhan BS Giridhar R Menard R 《Journal of enzyme inhibition and medicinal chemistry》2008,23(2):190-197
Cathepsins have been found to have important physiological roles. The implication of cathepsin L in various types of cancers is well established. In a search for selective cathepsin L inhibitors as anticancer agents, a series of 2-cyanoprrolidine peptidomimetics, carrying a nitrile group as warhead, were designed. Two series of compounds, one with a benzyl moiety and a second with an isobutyl moiety at P(2) position of the enzyme were synthesized. The synthesized compounds were evaluated for inhibitory activity against human cathepsin L and cathepsin B. Although, none of the compounds showed promising inhibitory activity, (E)N-{(S)1-[(S)2-cyano-1-pyrrolidinecarbonyl]-3-methylbutyl}-2,3-diphenylacrylamide (24) with an isobutyl moiety at P(2) was found to show selectivity as a cathepsin L inhibitor (Ki 5.3 microM for cathepsin L and Ki > 100 microM for cathepsin B). This compound could act as a new lead for the further development of improved inhibitors within this inhibitor type. 相似文献
53.
Oral candidiasis is the most common opportunistic infection in individuals infected with the human immunodeficiency virus. Though Candida albicans is the major aetiological agent, non-albicans species such Candida tropicalis are now emerging as important agents of such infection. The Candida cell surface hydrophobicity (CSH) is considered a critical factor contributing to its colonization potential and virulence. It is also known that brief exposure to sub-cidal concentrations of antifungal agents is a likely scenario in the oral environment where the administered drugs are diluted continuously due to the flushing action of saliva. Hence the objective of the present study was to compare the CSH of 10 isolates each of C. albicans and C. tropicalis from HIV-infected individuals following brief exposure (1hour) of isolates to sub-therapeutic concentrations of nystatin, amphotericin B, ketoconazole, fluconazole and 5-flurocytosine. The CSH was assessed by a previously described biphasic aqueous-hydrocarbon assay. The mean percentage reduction of CSH of C. albicans following brief exposure to nystatin, amphotericin B, ketoconazole, fluconazole and 5-flurocytosine was27.33 (p < 0.001), 21.34 (p < 0.05), 11.74 (p > 0.05), 18.4 (p > 0.05) and 14.64 (p > 0.05) respectively. The mean percentage reduction of CSH of C. tropicalis following brief exposure to nystatin, amphotericin B, ketoconazole, fluconazole and 5-flurocytosine was 33.81 (p < 0.01), 28.88 (p < 0.01), 12.6 (p > 0.05), 21.53(p > 0.05) and 17.68 (p > 0.05) respectively. A significant inter-species variation in CSH was observed for nystatin and amphoterecin B. Overall the results reveal that the CSH of C. albicans is affected to a significantly lesser degree compared with C. tropicalis when exposed to the antifungals. These data further illustrate another mode of action of antifungals on Candida leading to a reduction in the CSH and thereby the yeast adherence to host tissues. This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
54.
Benthic diatoms, which often dominate marine biofilms are mostly pennate along with a few centric species that have an attached mode of life. Even though the range of diatoms in biofilms is diverse, their ecology is poorly understood because of the difficulty in sampling and enumeration. Scraping or brushing are the traditional methods used for removal of diatoms from biofilms developed on solid substrata. The method of removal is the most critical step in enumerating the biofilm diatom community structure. In this study, a nylon brush and ceramic scraper were used as tools for the removal of diatoms from 1 - 4-day-old biofilms developed on fibreglass coupons and glass microscope slides. Standardisation of methods showed that the sample volume used in the analyses had the least influence on the quantification, whereas the method of removal was critical. The nylon brush was more efficient at recovering diatoms compared to a ceramic scraper. Direct microscopic enumeration of the community in the case of glass slides indicated that scraping resulted in between 30-50% underestimation. Heterogeneity in diatom community structure between replicate samples is one possible reason for such underestimation. 相似文献
55.
Interaction between arbuscular mycorrhizal fungus Glomus deserticola and pteridophytic member Ampelopteris prolifera was found abundant on entire growth level based on elemental composition and gaseous exchange as a potential remediation system for phytoextraction of chromium. Inoculated A. prolifera (AM) and non-inoculated A. prolifera (Non-AM) were supplied with two Cr species: 12 mmol of trivalent cation (Cr+3) [Cr(III)] and 0.1 mmol of divalent dichromate anion (Cr2O7 ?2) [Cr(VI)]. Both Cr species were found to be depressed in overall growth and inefficient stomatal conductance (gs) and net photosynthesis (NP). Mycorrhizal association was found to be natural scavenger of Cr toxicity as indicated by greater growth in plants exposed to Cr species, and increased gas exchange of Cr(III) treated plants. Though, chromium reduction resulted lower level of nitrogen (N), phosphorus (P), and potassium (K) but interestingly elevated the level of aluminum (Al), iron (Fe), and zinc (Zn) uptake in many folds which is the significance of sustainable growth of plant. 相似文献
56.
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58.
Yaoyu Ren Timo Danner Alexandra Moy Martin Finsterbusch Tanner Hamann Jan Dippell Till Fuchs Marius Müller Ricky Hoft André Weber Larry A. Curtiss Peter Zapol Matthew Klenk Anh T. Ngo Pallab Barai Brandon C. Wood Rongpei Shi Liwen F. Wan Tae Wook Heo Martin Engels Jagjit Nanda Felix H. Richter Arnulf Latz Venkat Srinivasan Jürgen Janek Jeff Sakamoto Eric D. Wachsman Dina Fattakhova-Rohlfing 《Liver Transplantation》2023,13(1):2201939
The garnet-type phase Li7La3Zr2O12 (LLZO) attracts significant attention as an oxide solid electrolyte to enable safe and robust solid-state batteries (SSBs) with potentially high energy density. However, while significant progress has been made in demonstrating compatibility with Li metal, integrating LLZO into composite cathodes remains a challenge. The current perspective focuses on the critical issues that need to be addressed to achieve the ultimate goal of an all-solid-state LLZO-based battery that delivers safety, durability, and pack-level performance characteristics that are unobtainable with state-of-the-art Li-ion batteries. This perspective complements existing reviews of solid/solid interfaces with more emphasis on understanding numerous homo- and heteroionic interfaces in a pure oxide-based SSB and the various phenomena that accompany the evolution of the chemical, electrochemical, structural, morphological, and mechanical properties of those interfaces during processing and operation. Finally, the insights gained from a comprehensive literature survey of LLZO–cathode interfaces are used to guide efforts for the development of LLZO-based SSBs. 相似文献
59.
Irshad Ahmad Anil K. Sharma Henry Daniell Shashi Kumar 《Plant biotechnology journal》2015,13(4):540-550
Higher lipid biosynthesis and accumulation are important to achieve economic viability of biofuel production via microalgae. To enhance lipid content, Chlamydomonas reinhardtii was genetically engineered with a key enzyme diacylglycerol acyltransferase (BnDGAT2) from Brassica napus, responsible for neutral lipid biosynthesis. The transformed colonies harbouring aph7 gene, screened on hygromycin‐supplemented medium, achieved transformation frequency of ~120 ± 10 colonies/1 × 106 cells. Transgene integration and expression were confirmed by PCR, Southern blots, staining lipid droplets, proteins and spectro‐fluorometric analysis of Nile red‐stained cells. The neutral lipid is a major class (over 80% of total lipids) and most significant requirement for biodiesel production; this was remarkably higher in the transformed alga than the untransformed control. The levels of saturated fatty acids in the transformed alga decreased to about 7% while unsaturated fatty acids increased proportionately when compared to wild type cells. Polyunsaturated fatty acids, especially α‐linolenic acid, an essential omega‐3 fatty acid, were enhanced up to 12% in the transformed line. Nile red staining confirmed formation of a large number of lipid globules in the transformed alga. Evaluation of long‐term stability and vitality of the transgenic alga revealed that cryopreservation produced significantly higher quantity of lipid than those maintained continuously over 128 generations on solid medium. The overexpression of BnDGAT2 significantly altered the fatty acids profile in the transformed alga. Results of this study offer a valuable strategy of genetic manipulation for enhancing polyunsaturated fatty acids and neutral lipids for biofuel production in algae. 相似文献
60.
Hydroxylated analogues of the orally active broad spectrum antifungal, Sch 51048 (1), and the discovery of posaconazole [Sch 56592; 2 or (S,S)-5 总被引:1,自引:0,他引:1
Bennett F Saksena AK Lovey RG Liu YT Patel NM Pinto P Pike R Jao E Girijavallabhan VM Ganguly AK Loebenberg D Wang H Cacciapuoti A Moss E Menzel F Hare RS Nomeir A 《Bioorganic & medicinal chemistry letters》2006,16(1):186-190
As part of a detailed study, the syntheses, biological activities, and pharmacokinetic properties of hydroxylated analogues of the previously described broad spectrum antifungal agents, Sch 51048 (1), Sch 50001 (3), and Sch 50002 (4), are described. Based on an overall superior profile, one of the alcohols, Sch 56592 (2), was selected for clinical studies. 相似文献