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排序方式: 共有306条查询结果,搜索用时 15 毫秒
71.
Wada S Morishima-Kawashima M Qi Y Misono H Shimada Y Ohno-Iwashita Y Ihara Y 《Biochemistry》2003,42(47):13977-13986
Cholesterol has been claimed to be involved in the generation and/or accumulation of amyloid beta protein (Abeta). However, the underlying molecular mechanisms have not been fully elucidated yet. Here, we have investigated the effect of membrane cholesterol content on gamma-secretase activity using Chinese hamster ovary cells stably expressing beta-amyloid precursor protein (APP) and either wild-type or N141I mutant-type presenilin 2. Cholesterol was acutely depleted from the isolated membrane by methyl-beta-cyclodextrin, and Abeta production was assessed in a cell-free assay system. Reduced cholesterol did not significantly alter the amounts of Abeta produced by either total cell membranes or cholesterol-rich low-density membrane domains. Even its extremely low levels in the latter domains did not affect Abeta production. This indicates that the membrane cholesterol content does not directly modulate the activity of gamma-secretase. To ascertain that gamma-secretase resides in cholesterol-rich membrane domains, low-density membrane domains were further fractionated with BCtheta (biotinylated theta-toxin nicked with subtilisin Carlsberg protease), which has recently been shown to bind selectively to rafts of intact cells. The membrane domains purified with BCtheta did indeed produce Abeta. These observations indicate that the gamma-cleavage required for generating Abeta occurs in rafts, but its activity is virtually cholesterol-independent. 相似文献
72.
The addition of sialic acid to T cell surface glycoproteins influences essential T cell functions such as selection in the thymus and homing in the peripheral circulation. Sialylation of glycoproteins can be regulated by expression of specific sialyltransferases that transfer sialic acid in a specific linkage to defined saccharide acceptor substrates and by expression of particular glycoproteins bearing saccharide acceptors preferentially recognized by different sialyltransferases. Addition of alpha2,6-linked sialic acid to the Galbeta1,4GlcNAc sequence, the preferred ligand for galectin-1, inhibits recognition of this saccharide ligand by galectin-1. SAalpha2,6Gal sequences, created by the ST6Gal I enzyme, are present on medullary thymocytes resistant to galectin-1-induced death but not on galectin-1-susceptible cortical thymocytes. To determine whether addition of alpha2,6-linked sialic acid to lactosamine sequences on T cell glycoproteins inhibits galectin-1 death, we expressed the ST6Gal I enzyme in a galectin-1-sensitive murine T cell line. ST6Gal I expression reduced galectin-1 binding to the cells and reduced susceptibility of the cells to galectin-1-induced cell death. Because the ST6Gal I preferentially utilizes N-glycans as acceptor substrates, we determined that N-glycans are essential for galectin-1-induced T cell death. Expression of the ST6Gal I specifically resulted in increased sialylation of N-glycans on CD45, a receptor tyrosine phosphatase that is a T cell receptor for galectin-1. ST6Gal I expression abrogated the reduction in CD45 tyrosine phosphatase activity that results from galectin-1 binding. Sialylation of CD45 by the ST6Gal I also prevented galectin-1-induced clustering of CD45 on the T cell surface, an initial step in galectin-1 cell death. Thus, regulation of glycoprotein sialylation may control susceptibility to cell death at specific points during T cell development and peripheral activation. 相似文献
73.
Yvon Le Maho 《Polar Biology》1994,14(5):315-318
New technology, that is based on miniaturization of electronic equipment and progress in computers, now enables us to get data on the foraging behavior of Antarctic birds and mammals. This technical revolution is of a major scientific importance because until recently it was considered impossible to study where animals feed and how much they consume. Accordingly, feeding strategies may now be studied in relation to breeding status or availability in marine resources. This, in turn, facilitates the use of antarctic animals as indicators of the changes in these resources. Automatic indentification and weighing of breeding seabirds has also become possible. This means changes in their body condition, i.e. body fuel reserves and food stores at sea, can be monitored. Thus a short-term indication of the changes in the availability of some marine resources may now be obtained. These new methods represent a major advance because they open new research possibilities, whereby antarctic animals can be individually monitored or at a population level, ashore and at sea, while minimizing human disturbance.Paper presented at the Symposium on Polar regions: the challenge for biological and ecological research organized by the Swiss Committee for Polar Research, Basel on 2 October 1992 相似文献
74.
75.
Sébastien Descamps Michel Gauthier-Clerc Céline Le Bohec Jean-Paul Gendner Yvon Le Maho 《Polar Biology》2005,28(4):303-310
Predation can have major effects on population dynamics, but predator–prey interactions in marine ecosystems have rarely been studied. While the king penguin is one of the most studied seabirds, little is known about the impact of predation on its population dynamics. Here, we determine the impact of the main predators (giant petrels and skuas) on king penguin breeding success taking into account the nocturnal predation of petrels. We found that predation is the most important source of breeding failure for king penguins. The smallest chicks within crèches are the most hunted. The periphery of the colony suffers the highest risk of predation during summer. Our study shows the unequal quality of some areas inside the colony in terms of predation risk and breeding success, and points out the importance of timing in successful breeding. 相似文献
76.
Shiratori I Yamaguchi M Suzukawa M Yamamoto K Lanier LL Saito T Arase H 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(7):4441-4449
Human and rodent CD200 are recognized by the inhibitory CD200R, and these molecules play an important role in the regulation of the immune system. Several viruses, such as human herpesvirus-6 (HHV-6), HHV-7, and HHV-8, possess a CD200 homologue, suggesting that these viruses regulate the immune response via CD200R. In this study, we analyzed the effect of human CD200 and the viral CD200 homologues on human CD200R-expressing cells. We found that human CD200R is predominantly expressed on basophils in amounts higher than on other human peripheral blood leukocytes. Furthermore, the viral CD200 homologues as well as human CD200 were recognized by human CD200R, and the activation of basophils was down-regulated by these CD200 proteins. These results suggested that CD200R is an important regulatory molecule of basophil activation. In addition, the presence of CD200 homologues on several viruses suggests a potentially unique relationship between basophil function and viral infection. 相似文献
77.
Nishiwaki K Kubota Y Chigira Y Roy SK Suzuki M Schvarzstein M Jigami Y Hisamoto N Matsumoto K 《Nature cell biology》2004,6(1):31-37
In the nematode Caenorhabditis elegans, the gonad acquires two U-shaped arms through the directed migration of its distal tip cells (DTCs), which are located at the tip of the growing gonad arms. A member of the ADAM (a disintegrin and metalloprotease) family, MIG-17, regulates directional migration of DTCs: MIG-17 is synthesized and secreted from the muscle cells of the body wall, and diffuses to the gonad where it is required for DTC migration. The mig-23 mutation causes defective migration of DTCs and interacts genetically with mig-17. Here, we report that mig-23 encodes a membrane-bound nucleoside diphosphatase (NDPase) required for glycosylation and proper localization of MIG-17. Our findings indicate that an NDPase affects organ morphogenesis through glycosylation of the MIG-17 ADAM protease. 相似文献
78.
79.
Masami Suzuki Fumiko Chiwaki Yumi Sawada Maho Ashikawa Kazuhiko Aoyagi Takeshi Fujita Kazuyoshi Yanagihara Masayuki Komatsu Minoru Narita Tsutomu Suzuki Hiroshi Nagase Ryoji Kushima Hiromi Sakamoto Takeo Fukagawa Hitoshi Katai Hitoshi Nakagama Teruhiko Yoshida Yasuhito Uezono Hiroki Sasaki 《PloS one》2015,10(4)
The dormancy of tumor cells is a major problem in chemotherapy, since it limits the therapeutic efficacy of anti-tumor drugs that only target dividing cells. One potential way to overcome chemo-resistance is to “wake up” these dormant cells. Here we show that the opioid antagonist methylnaltrexone (MNTX) enhances the effect of docetaxel (Doc) by blocking a cell growth-suppressive pathway. We found that PENK, which encodes opioid growth factor (OGF) and suppresses cell growth, is predominantly expressed in diffuse-type gastric cancers (GCs). The blockade of OGF signaling by MNTX releases cells from their arrest and boosts the effect of Doc. In comparison with the use of Doc alone, the combined use of Doc and MNTX significantly prolongs survival, alleviates abdominal pain, and diminishes Doc-resistant spheroids on the peritoneal membrane in model mice. These results suggest that blockade of the pathways that suppress cell growth may enhance the effects of anti-tumor drugs. 相似文献