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991.
Chen JX Zeng H Tuo QH Yu H Meyrick B Aschner JL 《American journal of physiology. Heart and circulatory physiology》2007,292(4):H1664-H1674
Recent studies have demonstrated that reactive oxygen species (ROS) mediate myocardial ischemia-reperfusion (I/R) and angiogenesis via the mitogen-activated protein kinases and the serine-threonine kinase Akt/protein kinase B pathways. NADPH oxidases are major sources of ROS in endothelial cells and cardiomyocytes. In the present study, we investigated the role of NADPH oxidase-derived ROS in hypoxia-reoxygenation (H/R)-induced Akt and ERK1/2 activation and angiogenesis using porcine coronary artery endothelial cells (PCAECs) and a mouse myocardial I/R model. Our data demonstrate that exposure of PCAECs to hypoxia for 2 h followed by 1 h of reoxygenation significantly increased ROS formation. Pretreatment with the NADPH oxidase inhibitors, diphenyleneiodonium (DPI, 10 microM) and apocynin (Apo, 200 and 600 microM), significantly attenuated H/R-induced ROS formation. Furthermore, exposure of PCAECs to H/R caused a significant increase in Akt and ERK1/2 activation. Exposure of PCAEC spheroids and mouse aortic rings to H/R significantly increased endothelial spheroid sprouting and vessel outgrowth, whereas pharmacological inhibition of NADPH oxidase or genetic deletion of the NADPH oxidase subunit, p47(phox) (p47(phox-/-)), significantly suppressed these changes. With the use of a mouse I/R model, our data further show that the increases in myocardial Akt and ERK1/2 activation and vascular endothelial growth factor (VEGF) expression were markedly blunted in the p47(phox-/-) mouse subjected to myocardial I/R compared with the wild-type mouse. Our findings underscore the important role of NADPH oxidase and its subunit p47(phox) in modulating Akt and ERK1/2 activation, angiogenic growth factor expression, and angiogenesis in myocardium undergoing I/R. 相似文献
992.
Despite the recognition that increased suspended sediment concentration (SSC) is a correlate of imperilment for native riverine
fishes, research is limited on the effects of SSC on small non-game species. This study quantifies the impact of suspended
sediment on fish growth and gill condition of two stream-dwelling minnows. Specific growth rate (i.e., percent change in mass
per day) and gill condition (i.e., lamellar thickness and interlamellar area) were measured in young-of-year whitetail shiners,
Cyprinella galactura, and federally threatened spotfin chubs, Erimonax
monachus, exposed for 21 days to increased SSC (0, 25, 50, 100, and 500 mg L−1). Exposure to elevated SSC caused a significant decrease in specific growth rate in both species and at all life stages tested.
The effect of increased SSC was greatest in spotfin chubs, which exhibited a 15-fold decrease in specific growth rate at the
highest treatment (500 mg L−1). Effects of increased SSC were least for 8–9-month-old whitetail shiners, which had growth rates similar to controls for
25, 50, and 100 mg L−1 treatments. These minnows exhibited a greater response to increasing SSC than salmonids at low to moderate SSC, and a lesser
response at higher sediment levels. Gill damage was minimal at the three lowest treatment levels, moderate at 100 mg L−1 and severe at 500 mg L−1, indicating that respiratory surfaces of upland minnows may be much more sensitive than other species. Specific growth rate
decreased significantly with increasing gill lamellar thickness, suggesting that respiratory impairment is one mechanism responsible
for negative impacts of excessive sediment on small riverine fishes. 相似文献
993.
994.
995.
Elizabeth O'Day Minh T. N. Le Shunsuke Imai Shen Mynn Tan Rory Kirchner Haribabu Arthanari Oliver Hofmann Gerhard Wagner Judy Lieberman 《The Journal of biological chemistry》2015,290(29):17909-17922
Lin28 is an evolutionarily conserved RNA-binding protein that inhibits processing of pre-let-7 microRNAs (miRNAs) and regulates translation of mRNAs that control developmental timing, pluripotency, metabolism, and tumorigenesis. The RNA features that mediate Lin28 binding to the terminal loops of let-7 pre-miRNAs and to Lin28-responsive elements (LREs) in mRNAs are not well defined. Here we show that Lin28 target datasets are enriched for RNA sequences predicted to contain stable planar structures of 4 guanines known as G-quartets (G4s). The imino NMR spectra of pre-let-7 loops and LREs contain resonances characteristic of G4 hydrogen bonds. These sequences bind to a G4-binding fluorescent dye, N-methyl-mesoporphyrin IX (NMM). Mutations and truncations in the RNA sequence that prevent G4 formation also prevent Lin28 binding. The addition of Lin28 to a pre-let-7 loop or an LRE reduces G4 resonance intensity and NMM binding, suggesting that Lin28 may function to remodel G4s. Further, we show that NMM inhibits Lin28 binding. Incubation of a human embryonal carcinoma cell line with NMM reduces its stem cell traits. In particular it increases mature let-7 levels, decreases OCT4, HMGA1, CCNB1, CDK4, and Lin28A protein, decreases sphere formation, and inhibits colony formation. Our results suggest a previously unknown structural feature of Lin28 targets and a new strategy for manipulating Lin28 function. 相似文献
996.
Yusuke Komiya Judy E. Anderson Mariko Akahoshi Mako Nakamura Ryuichi Tatsumi Yoshihide Ikeuchi Wataru Mizunoya 《Analytical biochemistry》2015
To attain a superior in vitro model of mature muscle fibers, we modified the established protocol for isolating single muscle fibers from rat skeletal muscle. Muscle fiber cultures with high viability were obtained using flexor digitorum brevis muscle and lasted for at least 7 days. We compared the expression levels of adult myosin heavy chain (MyHC) isoforms in these single muscle fibers with myotubes formed from myoblasts; isolated fibers contained markedly more abundant adult MyHC isoforms than myotubes. This muscle fiber model, therefore, will be useful for studying the various functions and cellular processes of mature muscles in vitro. 相似文献
997.
998.
Alexis R. Demonbreun Kaitlin E. Swanson Ann E. Rossi H. Kieran Deveaux Judy U. Earley Madison V. Allen Priyanka Arya Sohinee Bhattacharyya Hamid Band Peter Pytel Elizabeth M. McNally 《PloS one》2015,10(9)
We previously showed that Eps15 homology domain-containing 1 (EHD1) interacts with ferlin proteins to regulate endocytic recycling. Myoblasts from Ehd1-null mice were found to have defective recycling, myoblast fusion, and consequently smaller muscles. When expressed in C2C12 cells, an ATPase dead-EHD1 was found to interfere with BIN1/amphiphysin 2. We now extended those findings by examining Ehd1-heterozygous mice since these mice survive to maturity in normal Mendelian numbers and provide a ready source of mature muscle. We found that heterozygosity of EHD1 was sufficient to produce ectopic and excessive T-tubules, including large intracellular aggregates that contained BIN1. The disorganized T-tubule structures in Ehd1-heterozygous muscle were accompanied by marked elevation of the T-tubule-associated protein DHPR and reduction of the triad linker protein junctophilin 2, reflecting defective triads. Consistent with this, Ehd1-heterozygous muscle had reduced force production. Introduction of ATPase dead-EHD1 into mature muscle fibers was sufficient to induce ectopic T-tubule formation, seen as large BIN1 positive structures throughout the muscle. Ehd1-heterozygous mice were found to have strikingly elevated serum creatine kinase and smaller myofibers, but did not display findings of muscular dystrophy. These data indicate that EHD1 regulates the maintenance of T-tubules through its interaction with BIN1 and links T-tubules defects with elevated creatine kinase and myopathy. 相似文献
999.
Studies of dietary fat absorption are generally conducted by using an animal model equipped with a lymph cannula. Although this animal model is widely accepted as the in vivo model of dietary fat absorption, the surgical techniques involved are challenging and expensive. Genetic manipulation of the animal model is also costly and time consuming. The alternative in vitro model is arguably more affordable, timesaving, and less challenging. Importantly, the in vitro model allows investigators to examine the enterocytes as an isolated system, reducing the complexity inherent in the whole organism model. This paper describes how human colon carcinoma cells (Caco-2) can serve as an in vitro model to study the enterocyte transport of lipids, and lipid-soluble drugs and vitamins. It explains the proper maintenance of Caco-2 cells and the preparation of their lipid mixture; and it further discusses the valuable option of using the permeable membrane system. Since differentiated Caco-2 cells are polarized, the main advantage of using the permeable membrane system is that it separates the apical from the basolateral compartment. Consequently, the lipid mixture can be added to the apical compartment while the lipoproteins can be collected from the basolateral compartment. In addition, the effectiveness of the lentivirus expression system in upregulating gene expression in Caco-2 cells is discussed. Lastly, this paper describes how to confirm the successful isolation of intestinal lipoproteins by transmission electron microscopy (TEM). 相似文献
1000.
Michael Hornsby Marcin Paduch Shane Miersch Annika S??f Tet Matsuguchi Brian Lee Karolina Wypisniak Allison Doak Daniel King Svitlana Usatyuk Kimberly Perry Vince Lu William Thomas Judy Luke Jay Goodman Robert J. Hoey Darson Lai Carly Griffin Zhijian Li Franco J. Vizeacoumar Debbie Dong Elliot Campbell Stephen Anderson Nan Zhong Susanne Gr?slund Shohei Koide Jason Moffat Sachdev Sidhu Anthony Kossiakoff James Wells 《Molecular & cellular proteomics : MCP》2015,14(10):2833-2847