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151.
17β-Hydroxysteroid dehydrogenase type 11 (17βHSD11) is mostly localized on the endoplasmic reticulum (ER) membrane under normal conditions and redistributes to lipid droplets (LDs) when the formation of LDs is induced. In this study, confocal microscopy analyses of the subcellular localization of the mutated 17βHSD11 proteins in cells with or without LDs revealed that both an N-terminal hydrophobic sequence and an adjacent sequence that has a weak homology with the PAT motif are independently necessary and both parts together (28 amino acid residues in total) are sufficient for the dual localization of 17βHSD11. Mutation analyses suggest that the PAT-like motif in 17βHSD11 will not be functionally similar to the canonical PAT motif. Hsp60 was identified as a possibly interacting protein with the PAT-like motif, and biochemical and microscopic analyses suggest that Hsp60 may be partly, but not necessarily involved in recognition of the PAT-like part of the targeting sequence of 17βHSD11. 相似文献
152.
Sho Morioka Peter Broglie Emily Omori Yuka Ikeda Giichi Takaesu Kunihiro Matsumoto Jun Ninomiya-Tsuji 《The Journal of cell biology》2014,204(4):607-623
TNF activates three distinct intracellular signaling cascades leading to cell survival, caspase-8–mediated apoptosis, or receptor interacting protein kinase 3 (RIPK3)–dependent necrosis, also called necroptosis. Depending on the cellular context, one of these pathways is activated upon TNF challenge. When caspase-8 is activated, it drives the apoptosis cascade and blocks RIPK3-dependent necrosis. Here we report the biological event switching to activate necrosis over apoptosis. TAK1 kinase is normally transiently activated upon TNF stimulation. We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation. In addition, we also demonstrated that activation of RIPK1 and RIPK3 promoted TAK1 activation, suggesting a positive feedforward loop of RIPK1, RIPK3, and TAK1. Conversely, ablation of TAK1 caused caspase-dependent apoptosis, in which Ripk3 deletion did not block cell death either in vivo or in vitro. Our results reveal that TAK1 activation drives RIPK3-dependent necrosis and inhibits apoptosis. TAK1 acts as a switch between apoptosis and necrosis. 相似文献
153.
Amanda D. Melin Yuka Matsushita Gillian L. Moritz Nathaniel J. Dominy Shoji Kawamura 《Proceedings. Biological sciences / The Royal Society》2013,280(1759)
Tarsiers are small nocturnal primates with a long history of fuelling debate on the origin and evolution of anthropoid primates. Recently, the discovery of M and L opsin genes in two sister species, Tarsius bancanus (Bornean tarsier) and Tarsius syrichta (Philippine tarsier), respectively, was interpreted as evidence of an ancestral long-to-middle (L/M) opsin polymorphism, which, in turn, suggested a diurnal or cathemeral (arrhythmic) activity pattern. This view is compatible with the hypothesis that stem tarsiers were diurnal; however, a reversion to nocturnality during the Middle Eocene, as evidenced by hyper-enlarged orbits, predates the divergence of T. bancanus and T. syrichta in the Late Miocene. Taken together, these findings suggest that some nocturnal tarsiers possessed high-acuity trichromatic vision, a concept that challenges prevailing views on the adaptive origins of the anthropoid visual system. It is, therefore, important to explore the plausibility and antiquity of trichromatic vision in the genus Tarsius. Here, we show that Sulawesi tarsiers (Tarsius tarsier), a phylogenetic out-group of Philippine and Bornean tarsiers, have an L opsin gene that is more similar to the L opsin gene of T. syrichta than to the M opsin gene of T. bancanus in non-synonymous nucleotide sequence. This result suggests that an L/M opsin polymorphism is the ancestral character state of crown tarsiers and raises the possibility that many hallmarks of the anthropoid visual system evolved under dim (mesopic) light conditions. This interpretation challenges the persistent nocturnal–diurnal dichotomy that has long informed debate on the origin of anthropoid primates. 相似文献
154.
Takumi Yamane Yuka Morioka Yasuyuki Kitaura Ken Iwatsuki Yoshiharu Shimomura 《Bioscience, biotechnology, and biochemistry》2018,82(4):611-615
AbstractBranched-chain amino acids (BCAAs) exhibit many physiological functions. However, the potential link and mechanism between BCAA and skin function are unknown. We examined the effects of deletion of branched-chain α-keto acid dehydrogenase kinase (BDK), a key enzyme in BCAA catabolism, on type I and III tropocollagen syntheses in mice. Leucine and isoleucine levels were significantly lower in the skin of BDK-KO mice compared with wild-type mice. No changes in valine concentrations were observed. The levels of type I and III tropocollagen proteins and mRNAs (COL1A1 and COL3A1) were significantly lower in the skin of BDK-KO mice compared with wild-type mice. The phosphorylation of p70 S6 kinase, which indicates mammalian target of rapamycin (mTOR) activation, was reduced in the skin of BDK-KO mice compared with wild-type mice. These findings suggest that deficiencies of leucine and isoleucine reduce type I and III tropocollagen syntheses in skin by suppressing the action of mTOR. 相似文献
155.
G. Yasuzumi T. Sawada R. Sugihara M. Kiriyama Misako Sugioka 《Cell and tissue research》1958,48(1):10-23
Summary On the basis of electron microscopy of nucleoli in various physiological stages of similar and different cells, it is assumed that the nucleolonemata appear for the first time in the pre-mitotic stage and subsequently the nucleolus-associated body makes its appearance.The nucleolonema is composed of helically coiled filaments 50 Å in diameter.The nucleolus-associated body comprises tightly packed filaments about 15–30 Å thick which are helically coiled. 相似文献
156.
Megumi Narukawa‐Nara Ayako Nakamura Ko Kikuzato Yusuke Kakei Akiko Sato Yuka Mitani Yumiko Yamasaki‐Kokudo Takahiro Ishii Ken‐ichiro Hayashi Tadao Asami Takehiko Ogura Shigeo Yoshida Shozo Fujioka Takashi Kamakura Tsutomu Kawatsu Masanori Tachikawa Kazuo Soeno Yukihisa Shimada 《The Plant journal : for cell and molecular biology》2016,87(3):245-257
We previously reported l ‐α‐aminooxy‐phenylpropionic acid (AOPP) to be an inhibitor of auxin biosynthesis, but its precise molecular target was not identified. In this study we found that AOPP targets TRYPTOPHAN AMINOTRANSFERASE of ARABIDOPSIS 1 (TAA1). We then synthesized 14 novel compounds derived from AOPP to study the structure–activity relationships of TAA1 inhibitors in vitro. The aminooxy and carboxy groups of the compounds were essential for inhibition of TAA1 in vitro. Docking simulation analysis revealed that the inhibitory activity of the compounds was correlated with their binding energy with TAA1. These active compounds reduced the endogenous indole‐3‐acetic acid (IAA) content upon application to Arabidopsis seedlings. Among the compounds, we selected 2‐(aminooxy)‐3‐(naphthalen‐2‐yl)propanoic acid (KOK1169/AONP) and analyzed its activities in vitro and in vivo. Arabidopsis seedlings treated with KOK1169 showed typical auxin‐deficient phenotypes, which were reversed by exogenous IAA. In vitro and in vivo experiments indicated that KOK1169 is more specific for TAA1 than other enzymes, such as phenylalanine ammonia‐lyase. We further tested 41 novel compounds with aminooxy and carboxy groups to which we added protection groups to increase their calculated hydrophobicity. Most of these compounds decreased the endogenous auxin level to a greater degree than the original compounds, and resulted in a maximum reduction of about 90% in the endogenous IAA level in Arabidopsis seedlings. We conclude that the newly developed compounds constitute a class of inhibitors of TAA1. We designated them ‘pyruvamine’. 相似文献
157.
158.
159.
Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats 总被引:2,自引:0,他引:2
Abe H Uto H Takami Y Takahama Y Hasuike S Kodama M Nagata K Moriuchi A Numata M Ido A Tsubouchi H 《Biochemical and biophysical research communications》2007,356(3):610-615
The role of osteoactivin (OA) in liver fibrogenesis remains unclear. After feeding wild-type (WT) and OA transgenic (OA-Tg) rats a choline-deficient, L-amino acid-defined (CDAA) diet for 12 weeks, we evaluated liver fibrosis. Hepatic fibrosis and expression of alpha-smooth muscle actin protein in OA-Tg rats were reduced in comparison to WT rats. Our examination of the expression of 31,100 genes by microarray analysis identified 177 and 256 genes that were upregulated and downregulated, respectively, by at least twofold in OA-Tg rat livers in comparison to WT rat livers. Of these genes, we confirmed a significant downregulation in the expression levels of tissue inhibitor of metalloproteinase-1 and -2, type I collagen, and platelet-derived growth factor receptor-alpha and -beta in the livers of OA-Tg rats. These results indicate that transgenic OA expression attenuates the development of hepatic fibrosis in association with the suppression of specific genes involved in its pathogenesis. 相似文献
160.
Matsushita-Ishiodori Y Yamanaka K Ogura T 《Biochemical and biophysical research communications》2007,359(1):157-162
Mutations in human spastin (SPG4) cause an autosomal dominant form of hereditary spastic paraplegia. Sequence analysis revealed that spastin contains the AAA (ATPases associated with diverse cellular activities) domain in the C-terminal region. Recently, it was reported that spastin interacts dynamically with microtubules and displays microtubule-severing activity. A plausible Caenorhabditis elegans homologue of spastin (SPAS-1) has been identified by homology search and phylogenetic analyses. To understand the function of the spastin homologue, we characterized the spas-1 deletion mutant and analyzed spas-1 expression regulation in C. elegans. SPAS-1 was localized with cytoskeletons at the perinuclear region. We found that microtubules were intensely stained at the centrosomal region in the deletion mutant. Furthermore, overexpression of SPAS-1 caused disassembly of microtubule network in cultured cells, while ATPase-deficient SPAS-1 did not. These results indicate that C. elegans SPAS-1 plays an important role in microtubule dynamics. We also found that two kinds of products were generated from spas-1 by alternative splicing in a developmental stage-dependent manner. 相似文献