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121.
Luong Cong Thuc Yasushi Teshima Naohiko Takahashi Yasuko Nagano-Torigoe Kaori Ezaki Kunio Yufu Mikiko Nakagawa Masahide Hara Tetsunori Saikawa 《Apoptosis : an international journal on programmed cell death》2010,15(6):669-678
Reactive oxygen species (ROS) are important intracellular signaling molecules and are implicated in cardioprotective pathways
including ischemic preconditioning. Statins have been shown to have cardioprotective effects against ischemia/reperfusion
injury, however, the precise mechanisms remain to be elucidated. We hypothesized that ROS-mediated signaling cascade may be
involved in pravastatin-induced cardioprotection. Cultured rat cardiomyocytes were exposed to H2O2 for 30 min to induce cell injury. Pravastatin significantly suppressed H2O2-induced cell death evaluated by propidium iodide staining and the MTT assay. Incubation with pravastatin activated catalase,
and prevented a ROS burst induced by H2O2, which preserved mitochondrial membrane potential. Protective effects were induced very rapidly within 10 min, which was
concordant with the up-regulation of phosphorylated ERK1/2. L-NAME, 5HD, N-acetylcysteine (NAC) and staurosporine inhibited ERK1/2 phosphorylation and also reduced pravastatin-induced cardioprotection,
suggesting NO, mitochondrial KATP (mitoKATP) channels, ROS and PKC should be involved in the cardioprotective signaling. We also demonstrated that pravastatin moderately
up-regulated ROS generation in a 5HD-inhibitable manner. In isolated perfused rat heart experiments, pravastatin administered
10 min prior to no-flow global ischemia significantly improved left ventricular functional recovery, and also reduced infarct
size, which were attenuated by the treatment with NAC, 5HD, L-NAME or staurosporine. Administration of pravastatin from the
beginning of reperfusion also conferred cardioprotection. Pravastatin protected the cardiomyocytes against oxidative stress
by preventing the ROS burst and preserving mitochondrial function. Moderately up-regulated ROS production by mitoKATP channels opening is involved in the pro-survival signaling cascade activated by pravastatin. 相似文献
122.
Transposable elements (TEs) are major components of the intergenic regions of the genome. However, TE transposition has the potential to threaten the reproductive fitness of the organism; therefore, organisms have evolved specialized molecular systems to sense and repress the expression of TEs to stop them from jumping to other genomic loci. Emerging evidence suggests that Argonaute proteins play a critical role in this process, in collaboration with two types of cellular small RNAs: PIWI-interacting RNAs (piRNAs) of the germline and endogenous small interfering RNAs (endo-siRNAs) of the soma, both of which are transcribed from TEs themselves. 相似文献
123.
Matsuoka K Terabatake M Esumi Y Hatano K Terunuma D Kuzuhara H 《Biomacromolecules》2006,7(8):2284-2290
To enhance biological activities on the basis of the sugar cluster effect, a series of carbosilane dendrimers as core scaffolds for the construction of glycodendrimers was systematically synthesized from appropriate chlorosilanes by a combination of alkenylation and hydrosylation reactions. Those carbosilane dendrimers having terminal C=C double bonds underwent general hydroboration reactions to give corresponding primary polyols. Further transformations of the alcohols were then performed by mesylation followed by a displacement with NaBr to provide corresponding dendrimers with 4 to 36 bromine atoms at each terminal end. Assembly of trisaccharide moieties of globotriaosyl ceramide using alkyl halide-type carbosilane dendrimers as the core frame was conducted in liquid ammonia by a one-pot reaction involving selective removal of a benzyl group under the Birch reduction condition and subsequent S(N)2 reaction to yield a series of carbosilane dendrimers having appropriate numbers of trisaccharide moieties. These dendrimers have unique shapes and adequate numbers of terminal trisaccharide moieties. Some of the dendrimers showed unique biological activity against Stxs, which were produced by pathogenic Escherichia coli O157:H7. 相似文献
124.
Yamane-Ohnuki N Kinoshita S Inoue-Urakubo M Kusunoki M Iida S Nakano R Wakitani M Niwa R Sakurada M Uchida K Shitara K Satoh M 《Biotechnology and bioengineering》2004,87(5):614-622
To generate industrially applicable new host cell lines for antibody production with optimizing antibody-dependent cellular cytotoxicity (ADCC) we disrupted both FUT8 alleles in a Chinese hamster ovary (CHO)/DG44 cell line by sequential homologous recombination. FUT8 encodes an alpha-1,6-fucosyltransferase that catalyzes the transfer of fucose from GDP-fucose to N-acetylglucosamine (GlcNAc) in an alpha-1,6 linkage. FUT8(-/-) cell lines have morphology and growth kinetics similar to those of the parent, and produce completely defucosylated recombinant antibodies. FUT8(-/-)-produced chimeric anti-CD20 IgG1 shows the same level of antigen-binding activity and complement-dependent cytotoxicity (CDC) as the FUT8(+/+)-produced, comparable antibody, Rituxan. In contrast, FUT8(-/-)-produced anti-CD20 IgG1 strongly binds to human Fcgamma-receptor IIIa (FcgammaRIIIa) and dramatically enhances ADCC to approximately 100-fold that of Rituxan. Our results demonstrate that FUT8(-/-) cells are ideal host cell lines to stably produce completely defucosylated high-ADCC antibodies with fixed quality and efficacy for therapeutic use. 相似文献
125.
Takahashi M Gotoh Y Isagawa T Nishimura T Goyama E Kim HS Mukai H Ono Y 《Journal of biochemistry》2003,133(2):181-187
PKNalpha is a fatty acid- and Rho-activated serine/threonine protein kinase having a catalytic domain homologous to members of the protein kinase C family. Recently it was reported that PKNalpha is involved in the p38 mitogen-activated protein kinase (MAPK) signaling pathway. To date, however, how PKNalpha regulates the p38gamma MAPK signaling pathway is unclear. Here we demonstrate that PKNalpha efficiently phosphorylates MLTKalpha (MLK-like mitogen-activated protein triple kinase), which was recently identified as a MAPK kinase kinase (MAPKKK) for the p38 MAPK cascade. Phosphorylation of MLTKalpha by PKNalpha enhances its kinase activity in vitro. Expression of the kinase-negative mutant of PKNalpha inhibited the mobility shift of MLTKalpha caused by osmotic shock in SDS-PAGE. Furthermore, PKNalpha associates with each member of the p38gamma MAPK signaling pathway (p38gamma, MKK6, and MLTKalpha). These results suggest that PKNalpha functions as not only an upstream activator of MLTKalpha but also a putative scaffold protein for the p38gamma MAPK signaling pathway. 相似文献
126.
Ozeki Y Chikagawa Y Kimura S Soh HC Maeda K Pornsiriwong W Kato M Akimoto H Oyanagi M Fukuda T Koda T Itoh Y Yamada A Davies E Ueno H Takeda J 《Journal of plant research》2003,116(2):155-159
Deletion mutants of the carrot phenylalanine ammonia-lyase gene promoter were used to survey cis-elements for their effect on expression of promoter activity by transient expression. Two putative cis-elements were required to give full activity, but a third might be the most important in regulation of the promoter by 2,4-dichlorophenoxyacetic
acid.
Electronic Publication 相似文献
127.
128.
Centrosomal proteins CG-NAP and kendrin provide microtubule nucleation sites by anchoring gamma-tubulin ring complex
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Takahashi M Yamagiwa A Nishimura T Mukai H Ono Y 《Molecular biology of the cell》2002,13(9):3235-3245
Microtubule assembly is initiated by the gamma-tubulin ring complex (gamma-TuRC). In yeast, the microtubule is nucleated from gamma-TuRC anchored to the amino-terminus of the spindle pole body component Spc110p, which interacts with calmodulin (Cmd1p) at the carboxy-terminus. However, mammalian protein that anchors gamma-TuRC remains to be elucidated. A giant coiled-coil protein, CG-NAP (centrosome and Golgi localized PKN-associated protein), was localized to the centrosome via the carboxyl-terminal region. This region was found to interact with calmodulin by yeast two-hybrid screening, and it shares high homology with the carboxyl-terminal region of another centrosomal coiled-coil protein, kendrin. The amino-terminal region of either CG-NAP or kendrin indirectly associated with gamma-tubulin through binding with gamma-tubulin complex protein 2 (GCP2) and/or GCP3. Furthermore, endogenous CG-NAP and kendrin were coimmunoprecipitated with each other and with endogenous GCP2 and gamma-tubulin, suggesting that CG-NAP and kendrin form complexes and interact with gamma-TuRC in vivo. These proteins were localized to the center of microtubule asters nucleated from isolated centrosomes. Pretreatment of the centrosomes by antibody to CG-NAP or kendrin moderately inhibited the microtubule nucleation; moreover, the combination of these antibodies resulted in stronger inhibition. These results imply that CG-NAP and kendrin provide sites for microtubule nucleation in the mammalian centrosome by anchoring gamma-TuRC. 相似文献
129.
Protein kinase CK1 (formerly termed casein kinase I) is ubiquitous in eukaryotic cells and comprises a family of as many as 14 isoforms (including splice variants) in mammalian cells. Mammalian CK1delta and CK1epsilon, which are highly related to each other, are enriched at the centrosomes in interphase cells and at the spindle during mitosis. In the present study we have isolated, using the yeast two-hybrid system, a 182 amino acid residue fragment of the centrosomal and golgi N-kinase anchoring protein (CG-NAP, also known as AKAP450), which specifically interacts with CK1delta and CK1epsilon, but not with other CK1 isoforms. The 182 amino acid residue CG-NAP fragment, or full length CG-NAP, co-immunoprecipitates with CK1delta and CK1epsilon from mammalian cells. Consistent with this association, endogenous CG-NAP/AKAP450 and CK1delta co-localize in cells. Moreover, when expressed in the presence of CK1delta the 182 amino acid residue CG-NAP fragment adopts the same sub-cellular localization as CK1delta. Strikingly, attachment of the CG-NAP fragment to the plasma membrane is sufficient to re-localize a significant level of CK1delta to the membrane. These findings support a model in which sub-cellular localization of CK1delta/epsilon molecules at the centrosome is mediated, at least in part, through the action of CG-NAP/AKAP450 and provide a potential mechanism by which the contribution to cell cycle progression by CK1delta/epsilon may be regulated. 相似文献
130.
Uchiumi T Shimoda Y Tsuruta T Mukoyoshi Y Suzuki A Senoo K Sato S Kato T Tabata S Higashi S Abe M 《Plant & cell physiology》2002,43(11):1351-1358
Leguminous plants have both symbiotic and nonsymbiotic hemoglobin (sym- and nonsym-Hb) genes. Three symbiotic (LjLb1, 2, 3) and one nonsymbiotic (LjNSG1) Hb genes were isolated from a genomic library of Lotus japonicus MG20 Miyakojima. Two motif sequences (AAAGAT and CTCTT) critical for nodule specific expression were conserved on the 5'-upstream sequence of LjLb1, 2 and 3. The 5'-upstream region of LjNSG1 contained the sequence consensus for nonsym-Hb. RT-PCR with specific primer sets for each LjLb gene showed that all the sym-Hb genes (LjLb1, 2, 3) were expressed specifically and strongly in root nodules. The expression of LjLb1, 2 and 3 could not be detected in root, leaf or stem of a mature plant, whereas low level expression was detected in seedlings by RT-PCR. This suggests that sym-Hbs may have another unknown function besides being oxygen transporter for the microsymbiont in symbiotic nitrogen fixation. The expression of LjNSG1, examined with RT-PCR, was detected at low level in root, leaf and stem. The expression of LjNSG1 was enhanced in root nodules, whereas it was repressed in roots colonized by mycorrhizal fungi Glomus sp. R10. The repression of the nonsym-Hb gene was also observed in the roots of Medicago sativa colonized by Glomus sp. R10. 相似文献