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排序方式: 共有183条查询结果,搜索用时 15 毫秒
51.
Yukihiro Terada Seiichiro Nagai Tadashi Mabuchi Shuji Hirata Tomoko Shoda Tsuyoshi Kasai Kazuhiko Hoshi Sadaki Yokota Hiroshi Shitara Hiromichi Yonekawa Kaoru Yanagida Hideh Saito Koji Nakagawa Satoshi Kawachiya Wakako Iwasaki Mami Sato Megumu Ito Gabriera M. Ishida Yuji Takahashi Naoki Takeshita 《Human cell》2004,17(2):27-32
52.
Abstract: One of the pathological changes of Alzheimer's disease is the deposit of β/A4 protein, which is derived from Alzheimer amyloid precursor protein (APR). In the secretory pathway, APR is cleaved at an internal region of β/A4 protein by a hypothetical enzyme “secretase.” Our previous study showed that the site of cleavage of APR by secretase is determined by the length from the membrane-spanning region. To investigate the role of the transmem- brane region in APR secretion, we constructed the mutations of triplet lysine residues (Lys724-Lys725-Lys726), which are located just in the carboxyl region after the proposed membrane domain. The mutations were as follows: VVK, Val724-Val725-Lys726; LLI, Leu724-Leu725-lle726; and EEE, Glu724-Glu725-Glu726. Wild-type APR and mutant APPs were expressed transiently in COS-1 cells by cDNA trans-fection. The hydrophobic mutant VVK and LLI were processed and secreted in a way similar to that of the wild- type APR, although the rate of secretion was decreased. The acidic mutant EEE was not secreted into medium. Proteinase K treatment and cell surface biotinylation of the COS-1 cells expressing APR revealed that APR was located in the plasma membrane with a short intracellular carboxyl region. However, EEE was completely digested by proteinase K treatment, which suggested that the whole residues of this mutant are located at the outer surface of the cell, including its proposed membrane domain and carboxyl region. This mutant was not cleaved at all by secretase. These findings suggested that the triplet lysine residues of APR after the predicted membrane spanning domain play an important role in the membrane anchorage. In addition, the membrane anchorage was also important for the normal processing by secretase. 相似文献
53.
Acetaldehyde metabolism in human erythrocytes was studied using head-space gas chromatographic determination methods, and it was found that acetaldehyde is metabolized in erythrocytes by NAD dependent cytosolic enzyme having an apparent Km value for acetaldehyde approximately 0.7 mM at pH 7.4, and more than 50% of this activity was reduced by 1 μM disulfiram. So, it is suggested that erythrocytes may have an enzyme system similar to the high Km isozyme of the liver aldehyde dehydrogenase. 相似文献
54.
Summary Genetic polymorphism of the B subunit of human coagulation factor XIII was studied using agarose gel isoelectric focusing (pH 4–6.5) followed by immunofixation. Factor XIII-B of all samples after desialylation was classified into three types (F, S, and FS). From results of the present study, it was confirmed that factor XIII-B was controlled by two codominant alleles on an autosomal locus. Allele frequencies of F-XIIIB
F and F-XIIIB
S in a Japanese population were 0.336 and 0.664, respectively. 相似文献
55.
Midori Minami Tsutomu Takahashi Wakako Maruyama Akira Takahashi Philippe Dostert Toshiharu Nagatsu Makoto Naoi 《Journal of neurochemistry》1992,58(6):2097-2101
Salsolinol is one of the dopamine-derived tetrahydroisoquinolines and is synthesized from pyruvate or acetaldehyde and dopamine. As it cannot cross the blood-brain barrier, salsolinol as the R enantiomer in the brain is considered to be synthesized in situ in dopaminergic neurons. Effects of R and S enantiomers of salsolinol on kinetic properties of tyrosine hydroxylase [tyrosine, tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2], the rate-limiting enzyme of catecholamine biosynthesis, were examined. The naturally occurring cofactor of tyrosine hydroxylase, L-erythro-5,6,7,8-tetrahydrobiopterin, was found to induce allostery to the enzyme polymers and to change the affinity to the biopterin itself. Using L-erythro-5,6,7,8-tetrahydrobiopterin, tyrosine hydroxylase recognized the stereochemical structures of the salsolinols differently. The asymmetric center of salsolinol at C-1 played an important role in changing the affinity to L-tyrosine. The allostery of tyrosine hydroxylase toward biopterin cofactors disappeared, and at low concentrations of biopterin such as in brain tissue, the affinity to the cofactor changed markedly. A new type of inhibition of tyrosine hydroxylase, by depleting the allosteric effect of the endogenous biopterin, was found. It is suggested that under physiological conditions, such a conformational change may alter the regulation of DOPA biosynthesis in the brain. 相似文献
56.
In mitochondria, oxidative phosphorylation and enzymatic oxidation of biogenic amines by monoamine oxidase produce reactive
oxygen and nitrogen species, which are proposed to cause neuronal cell death in neurodegenerative disorders, including Parkinson’s
and Alzheimer’s disease. In these disorders, mitochondrial dysfunction, increased oxidative stress, and accumulation of oxidation-modified
proteins are involved in cell death in definite neurons. The interactions among these factors were studied by use of a peroxynitrite-generating
agent, N-morpholino sydnonimine (SIN-1) and an inhibitor of complex I, rotenone, in human dopaminergic SH-SY5Y cells. In control cells,
peroxynitrite nitrated proteins, especially the subunits of mitochondrial complex I, as 3-nitrotyrosine, suggesting that neurons
are exposed to constant oxidative stress even under physiological conditions. SIN-1 and an inhibitor of proteasome, carbobenzoxy-l-isoleucyl-γ-t-butyl-l-analyl-l-leucinal (PSI), increased markedly the levels of nitrated proteins with concomitant induction of apoptosis in the cells.
Rotenone induced mitochondrial dysfunction and accumulation and aggregation of proteins modified with acrolein, an aldehyde
product of lipid peroxidation in the cells. At the same time, the activity of the 20S β-subunit of proteasome was reduced
significantly, which degrades oxidative-modified protein. The mechanism was proved to be the result of the modification of
the 20S β-subunit with acrolein and to the binding of other acrolein-modified proteins to the 20S β-subunit.
Increased oxidative stress caused by SIN-1 treatment induced a decline in the mitochondrial membrane potential, ΔΨm, and activated
mitochondrial apoptotic signaling and induced cell death in SH-SY5Y cells. As another pathway, p38 mitogen-activated protein
(MAP) kinase and exracellular signal-regulated kinase (ERK) mediated apoptosis induced by SIN-1. On the other hand, a series
of neuroprotective propargylamine derivatives, including rasagiline [N-propargyl-1(R)aminoindan]and (−)deprenyl, intervened in the activation of apoptotic cascade by reactive oxygen species-reactive nitrogen
species in mitochondria through stabilization of the membrane potential, ΔΨm. In addition, rasagiline induced antiapoptotic
Bcl-2 and glial cell line-derived neurotrophic factor (GDNF) in SH-SY5Y cells, which was mediated by the ERK-nuclear factor
(NF)-κB pathway. These results are discussed in relation to the interaction of oxidative stress and mitochondria in the regulation
of neuronal death and survival in neurodegenerative diseases. 相似文献
57.
Kawakami Y Tsurugasaki W Nakamura S Osada K 《The Journal of nutritional biochemistry》2005,16(4):205-212
The effects of dietary soy isoflavones aglycone and glucoside on lipid metabolism were compared in male Sprague-Dawley rats (4 weeks old) given purified diets containing 0.3% cholesterol. The rats were fed a diet supplemented with either isoflavone aglycone-rich powder (IF-A group) or isoflavone glucoside-rich powder (IF-G group) or isoflavone-free diet (control group) for 40 days. The additional level of isoflavone aglycone moiety in the diet was prepared to the same level (approximately 0.096 g/100 g: approximately 0.1% in diet). The activity of hepatic cholesterol 7alpha-hydroxylase tended to be slightly higher in the rats fed isoflavones than in those fed the isoflavone-free diet. On the other hand, the activity of hepatic Delta6 desaturase in the IF-A group was lower than that of the control group. Reflecting this effect, the Delta6 desaturation indices [(20:3n-6+20:4n-6)/18:2n-6] in liver phospholipids of the IF-A group were lower than those in the control group. Liver and serum total cholesterol levels and liver TG level were also reduced by consumption of isoflavone aglycone. Moreover, serum TG level was lowered by consumption of both isoflavones aglycone and glucoside. The level of serum total isoflavones in the IF-A group was significantly higher than that in the IF-G group. Therefore, we speculate that the absorption speed of isoflavone aglycones might be faster than that of isoflavone glucosides in rats. This study suggests that dietary soy isoflavones, particularly their aglycone form, may exert a beneficial effect on lipid metabolism in rats fed cholesterol. 相似文献
58.
Ferri S Miura S Sakaguchi A Ishimura F Tsugawa W Sode K 《Marine biotechnology (New York, N.Y.)》2004,6(6):625-632
The gene encoding the fructosyl-amine oxidase (FAOD) from the marine yeast Pichia sp. N1-1 was cloned and expressed in Escherichia coli. Partial amino acid sequence analysis of the Pichia sp. N1-1 FAOD allowed the design of oligonucleotide primers for the amplification of the gene by inverse polymerase chain reaction. The FAOD gene was found to be devoid of introns and to encode a 48-kDa protein composed of 429 amino acid residues. The FAD-binding consensus sequence GXGXXG and the FAD covalent attachment-site cysteine residue have been identified within the predicted amino acid sequence. Comparisons with the amino acid sequences of other eukaryotic FAODs showed only 30% to 40% identities, establishing that the isolated Pichia N1-1 gene encodes a unique FAOD. Recombinant FAOD expression levels in E. coli reached 0.48 U/mg of soluble protein, which is considerably greater than native expression levels by inducing Pichia sp. N1-1 with fructosyl-valine (f-Val). The kinetic properties of the recombinant enzyme were almost indistinguishable from those of the native enzyme. We previously reported on the construction of a number of effective Pichia sp. N1-1 FAOD-based biosensors for measuring f-Val, a model compound for glycated hemoglobin. The further development of these biosensor systems can now greatly benefit from protein engineering and recombinant expression of the FAOD from Pichia N1-1.Note: The previous online version (January 20, 2005) of this article appeared with the legends of Figures 1 and 2 transposed. This version contains the figures with their appropriate legends. 相似文献
59.
60.
Keita Watanabe Shingo Kakeda Reiji Yoshimura Satoru Ide Kenji Hayashi Asuka Katsuki Wakako Umene-Nakano Rieko Watanabe Osamu Abe Yukunori Korogi 《PloS one》2015,10(11)
The effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR)-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects. 相似文献