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41.
The NH(2)-terminal transmembrane and lumenal domains of LGP85 are needed for the formation of enlarged endosomes/lysosomes 总被引:1,自引:0,他引:1
Kuronita T Hatano T Furuyama A Hirota Y Masuyama N Saftig P Himeno M Fujita H Tanaka Y 《Traffic (Copenhagen, Denmark)》2005,6(10):895-906
LGP85 is a lysosomal membrane protein possessing a type III topology and is also known as a member of the CD36 superfamily of proteins, such as CD36 and the scavenger-receptor BI (SR-BI). We have recently demonstrated that overexpression of LGP85 in various mammalian cell lines causes the enlargement of endosomal/lysosomal compartments (ELCs). Using chimeras and deletion mutants, we show here that the lumenal region of LGP85 is necessary, but not sufficient, for the development of ELCs. Effective formation of enlarged ELC was largely dependent on the presence of a preceding NH2 -terminal transmembrane segment. Analyses of deletion mutants within the lumenal domain further revealed a requirement of the NH2 -terminal transmembrane proximal lumenal region, with high sequence similarity with SR-BI for the enlargement of ELC. These results suggest that an interaction of the NH2 -terminal transmembrane proximal lumenal domain of LGP85 with the inner leaflet of endosomal/lysosomal membranes through the connection with the transmembrane domain is an essential determinant for the regulation of endosomal/lysosomal membrane traffic. Interestingly, although the NH2 -terminal transmembrane domain itself was not sufficient for the enlargement of ELCs, it appeared to be required for direct targeting of LGP85 from the trans -Golgi network to late endosomes/lysosomes. Taken together, these results indicate the involvement of distinct domain of LGP85 in the targeting to, and biogenesis and maintenance of, ELC. 相似文献
42.
Han F Takeda K Yokoyama S Ueda H Shinozawa Y Furuyama K Shibahara S 《Biochemical and biophysical research communications》2005,338(1):653-659
Heme oxygenase cleaves heme to form biliverdin, carbon monoxide (CO), and iron, and consists of two structurally related isozymes, HO-1 and HO-2. HO-2 is also known as a potential oxygen sensor. Here we show that the relative CO content in arterial blood, which reflects the total amount of endogenous heme degradation, dynamically changes in mice during acclimatization to normobaric hypoxia (10% O2), with the two peaks at 1 day and 21 days of hypoxia. The expression levels of HO-1 and HO-2 proteins were decreased by 20% and 40%, respectively, in the mouse liver at 7 days of hypoxia, which returned to the basal levels at 14 days. On the other hand, HO-1 and HO-2 proteins were increased 2-fold and 1.3-fold, respectively, in the heart at 28 days of hypoxia. Thus, hypoxia induces or represses the expression of HO-1 and HO-2 in vivo, depending on cellular microenvironments. 相似文献
43.
Fujita-Yoshigaki J Katsumata O Matsuki M Yoshigaki T Furuyama S Sugiya H 《Biochemical and biophysical research communications》2006,344(1):283-292
Secretory granules (SGs) are considered to be generated as immature granules and to mature by condensation of their contents. In this study, SGs of parotid gland were separated into low-, medium-, and high-density granule fractions by Percoll-density gradient centrifugation, since it was proposed that the density corresponds to the degree of maturation. The observation with electron microscopy showed that granules in the three fractions were very similar. The average diameter of high-density granules was a little but significantly larger than that of low-density granules. Although the three fractions contained amylase, suggesting that they are all SGs, distribution of membrane proteins was markedly different. Syntaxin6 and VAMP4 were localized in the low-density granule fraction, while VAMP2 was concentrated in the high-density granule fraction. Immunoprecipitation with anti-syntaxin6 antibody caused coprecipitation of VAMP2 from the medium-density granule fraction without solubilization, but not from Triton X-100-solubilized fraction, while VAMP4 was coprecipitated from both fractions. Therefore, VAMP2 is present on the same granules, but is separated from syntaxin6 and VAMP4, which are expected to be removed from immature granules. These results suggest that the medium-density granules are intermediates from low- to high-density granules, and that the membrane components of SGs dynamically change by budding and fusion during maturation. 相似文献
44.
Kamata M Yamashita T Kina A Tawada M Endo S Mizukami A Sasaki M Tani A Nakano Y Watanabe Y Furuyama N Funami M Amano N Fukatsu K 《Bioorganic & medicinal chemistry letters》2012,22(14):4769-4772
Spiro-pyrazolidinedione derivatives without quaternary chiral center were discovered by structure-based drug design and characterized as potent acetyl-CoA carboxylase (ACC) inhibitors. The high metabolic stability of the spiro-pyrazolo[1,2-a]pyridazine scaffold and enhancement of the activity by incorporation of a 7-methoxy group on the benzothiophene core successfully led to the identification of compound 4c as an orally bioavailable and highly potent ACC inhibitor. Oral administration of 4c significantly decreased the values of the respiratory quotient in rats, indicating the stimulation of fatty acid oxidation. 相似文献
45.
An endogenous inhibitor of the ADP-ribosylation of GTP-binding proteins by pertussis toxin is present in bovine brain 总被引:1,自引:0,他引:1
The ADP-ribosylation of GTP-binding proteins (G-proteins) catalyzed by pertussis toxin was inhibited by endogenous inhibitor activity in the membrane extract of bovine brain. Most of the activity appeared in the fractions eluted from a DEAE-Sephacel column by 0.5 M NaCl. The activity was heat-stable and sensitive to pronase K. The results suggest the presence of an endogenous inhibitor of pertussis toxin in bovine brain. 相似文献
46.
H Sugiya Y Fujita E Fukushima T Yamazaki S Furuyama 《The International journal of biochemistry》1988,20(3):237-241
1. Regulation of phosphofructokinase in rat submandibular gland was non-Michaelis-Menten type at physiological pH. 2. At pH 7.3, ATP played a dual role on phosphofructokinase acting as a substrate and inhibitor at high concentration of ATP. 3. The activator of phosphofructokinase was present in cytosol fraction, and its properties were resemble to those of fructose 2,6-bisphosphate. 4. Both the activator and authentic fructose 2,6-bisphosphate relieved the inhibition of phosphofructokinase by ATP, and increased the affinity for fructose 6-phosphate. 5. Concentration of fructose 2,6-bisphosphate in rat submandibular gland was 8.22 nmol/g tissue, and which was about the half of that in liver. 6. Phosphofructokinase in rat submandibular gland was found to be regulated synergistically by ATP, fructose 6-phosphate and fructose 2,6-bisphosphate. 相似文献
47.
Hara-Yokoyama M Nagatsuka Y Katsumata O Irie F Kontani K Hoshino S Katada T Ono Y Fujita-Yoshigaki J Sugiya H Furuyama S Hirabayashi Y 《Biochemistry》2001,40(4):888-895
Leukocyte cell surface antigen CD38 is a single-transmembrane protein whose extracellular domain has catalytic activity for NAD(+) glycohydrolase (NADase). We previously reported that b-series gangliosides inhibit the NADase activity of the extracellular domain of CD38 expressed as a fusion protein [Hara-Yokoyama, M., Kukimoto, I., Nishina, H., Kontani, K., Hirabayashi, Y., Irie, F., Sugiya, H., Furuyama, S., and Katada, T. (1996) J. Biol. Chem. 271, 12951-12955]. In the present study, we examined the effect of exogenous gangliosides on the NADase activity of CD38 on the surface of retinoic acid-treated human leukemic HL60 cells and CD38-transfected THP-1 cells. After incubation of the cells with G(T1b), inhibition of NADase activity was observed. The time course of inhibition was slower than that of the incorporation of G(T1b) into the cells, suggesting that incorporation into the cell membranes is a prerequisite for inhibition. Inhibition occurred efficiently when G(T1b) and CD38 were present on the same cells (cis interaction) rather than on different cells (trans interaction). Although gangliosides may affect localization of cell surface proteins, indirect immunofluorescence intensity due to CD38 was not affected after G(T1b) treatment. Comparison of the effect of G(T1b) and G(D1a) indicates that the tandem sialic acid residues linked to the internal galactose residue of the gangliotetraose core are crucial to the inhibition. These results suggest a novel role of complex gangliosides for the first time as cell surface inhibitors of CD38 through specific and cis interaction between the oligosaccharide moiety and the extracellular domain. 相似文献
48.
Fujioka S Masuda K Toguchi M Ohoka Y Sakai T Furuyama T Inagaki S 《Biochemical and biophysical research communications》2003,301(2):304-310
Semaphorins provide crucial attractive and repulsive cues involved in axon guidance during neural development. Out of them, Semaphorin 4D (Sema4D) is enriched in the nervous and immune tissues, and acts as proliferative and survival factors of peripheral lymphocytes in the immune system, but is poorly understood in the nervous system. By using PC12 cells which are well known to differentiate into neural cells in response to nerve growth factor (NGF), we found that soluble forms of Sema4D had neurotrophic effects which were inhibited by neutralizing antibodies to Sema4D. Sema4D strikingly potentiated neurite outgrowth in the presence of 50 ng/ml NGF and increased sensitivity to NGF. Cells responded to very low concentrations of NGF in the presence of 1 nM Sema4D. Activation of following signal proteins, protein kinase C (PKC), L-type of voltage-dependent Ca(2+) channel, and phosphatidylinositol (PI) 3-kinase mediated neurotrophic neurite-outgrowth action of Sema4D. These findings suggest a new function of Sema4D as a neurotrophic signal in PC12 cells. 相似文献
49.
Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload 下载免费PDF全文
Nakajima O Takahashi S Harigae H Furuyama K Hayashi N Sassa S Yamamoto M 《The EMBO journal》1999,18(22):6282-6289
Erythroid 5-aminolevulinate synthase (ALAS-E) catalyzes the first step of heme biosynthesis in erythroid cells. Mutation of human ALAS-E causes the disorder X-linked sideroblastic anemia. To examine the roles of heme during hematopoiesis, we disrupted the mouse ALAS-E gene. ALAS-E-null embryos showed no hemoglobinized cells and died by embryonic day 11.5, indicating that ALAS-E is the principal isozyme contributing to erythroid heme biosynthesis. In the ALAS-E-null mutant embryos, erythroid differentiation was arrested, and an abnormal hematopoietic cell fraction emerged that accumulated a large amount of iron diffusely in the cytoplasm. In contrast, we found typical ring sideroblasts that accumulated iron mostly in mitochondria in adult mice chimeric for ALAS-E-null mutant cells, indicating that the mode of iron accumulation caused by the lack of ALAS-E is different in primitive and definitive erythroid cells. These results demonstrate that ALAS-E, and hence heme supply, is necessary for differentiation and iron metabolism of erythroid cells. 相似文献
50.
Yuping Li Tomohiro Nishimura Kiichiro Teruya Tei Maki Takaaki Komatsu Takeki Hamasaki Taichi Kashiwagi Shigeru Kabayama Sun-Yup Shim Yoshinori Katakura Kazuhiro Osada Takeshi Kawahara Kazumichi Otsubo Shinkatsu Morisawa Yoshitoki Ishii Zbigniew Gadek Sanetaka Shirahata 《Cytotechnology》2002,40(1-3):139-149
Reactive oxygen species (ROS) cause irreversible damage to biological macromolecules, resulting in many diseases. Reduced
water (RW) such as hydrogen-rich electrolyzed reduced water and natural reduced waters like Hita Tenryosui water in Japan
and Nordenau water in Germany that are known to improve various diseases, could protect a hamster pancreatic β cell line,
HIT-T15 from alloxan-induced cell damage. Alloxan, a diabetogenic compound, is used to induce type 1 diabetes mellitus in
animals. Its diabetogenic effect is exerted via the production of ROS. Alloxan-treated HIT-T15 cells exhibited lowered viability,
increased intracellular ROS levels, elevated cytosolic free Ca2+ concentration, DNA fragmentation, decreased intracellular ATP levels and lowering of glucose-stimulated release of insulin.
RW completely prevented the generation of alloxan-induced ROS, increase of cytosolic Ca2+ concentration, decrease of intracellular ATP level, and lowering of glucose-stimulated insulin release, and strongly blocked
DNA fragmentation, partially suppressing the lowering of viability of alloxan-treated cells. Intracellular ATP levels and
glucose-stimulated insulin secretion were increased by RW to 2–3.5 times and 2–4 times, respectively, suggesting that RW enhances
the glucose-sensitivity and glucose response of β-cells. The protective activity of RW was stable at 4 °C for over a month,
but was lost by autoclaving. These results suggest that RW protects pancreatic β-cells from alloxan-induced cell damage by
preventing alloxan-derived ROS generation. RW may be useful in preventing alloxan-induced type 1-diabetes mellitus.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献