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171.
Hirobe T 《Pigment cell & melanoma research》2011,24(3):462-478
Coat colors are determined by melanin (eumelanin and pheomelanin). Melanin is synthesized in melanocytes and accumulates in special organelles, melanosomes, which upon maturation are transferred to keratinocytes. Melanocytes differentiate from undifferentiated precursors, called melanoblasts, which are derived from neural crest cells. Melanoblast/melanocyte proliferation and differentiation are regulated by the tissue environment, especially by keratinocytes, which synthesize endothelins, steel factor, hepatocyte growth factor, leukemia inhibitory factor and granulocyte-macrophage colony-stimulating factor. Melanocyte differentiation is also stimulated by alpha-melanocyte stimulating hormone; in the mouse, however, this hormone is likely carried through the bloodstream and not produced locally in the skin. Melanoblast migration, proliferation and differentiation are also regulated by many coat color genes otherwise known for their ability to regulate melanosome formation and maturation, pigment type switching and melanosome distribution and transfer. Thus, melanocyte proliferation and differentiation are not only regulated by genes encoding typical growth factors and their receptors but also by genes classically known for their role in pigment formation. 相似文献
172.
173.
Hiroyuki Suga Fumio Matsuda Tomohisa Hasunuma Jun Ishii Akihiko Kondo 《Applied microbiology and biotechnology》2013,97(4):1669-1678
Three enzymes responsible for the transhydrogenase-like shunt, including malic enzyme (encoded by MAE1), malate dehydrogenase (MDH2), and pyruvate carboxylase (PYC2), were overexpressed to regulate the redox state in xylose-fermenting recombinant Saccharomyces cerevisiae. The YPH499XU/MAE1 strain was constructed by overexpressing native Mae1p in the YPH499XU strain expressing xylose reductase and xylitol dehydrogenase from Scheffersomyces stipitis, and native xylulokinase. Analysis of the xylose fermentation profile under semi-anaerobic conditions revealed that the ethanol yield in the YPH499XU/MAE1 strain (0.38?±?0.01 g g?1 xylose consumed) was improved from that of the control strain (0.31?±?0.01 g g?1 xylose consumed). Reduced xylitol production was also observed in YPH499XU/MAE1, suggesting that the redox balance was altered by Mae1p overexpression. Analysis of intracellular metabolites showed that the redox imbalance during xylose fermentation was partly relieved in the transformant. The specific ethanol production rate in the YPH499XU/MAE1–MDH2 strain was 1.25-fold higher than that of YPH499XU/MAE1 due to the additional overexpression of Mdh2p, whereas the ethanol yield was identical to that of YPH499XU/MAE1. The specific xylose consumption rate was drastically increased in the YPH499XU/MAE1–MDH2–PYC2 strain. However, poor ethanol yield as well as increased production of xylitol was observed. These results demonstrate that the transhydrogenase function implemented in S. cerevisiae can regulate the redox state of yeast cells. 相似文献
174.
Ueyama H Horibe T Nakajima O Ohara K Kohno M Kawakami K 《Biochemical and biophysical research communications》2011,414(1):60-66
We previously reported that novel targeted “hybrid peptide” in which epidermal growth factor receptor (EGFR) binding peptide was conjugated with lytic-type peptide had selective cytotoxic activity to EGFR expressing cancer cells. In this study, we have generated a novel type hybrid peptide, semaphorin 3A lytic (Sema3A-lytic), which is composed of two functional amino acid domains: a sequence derived from Sema3A that binds to neuropilin-1 (NRP1) and a cytotoxic lytic peptide. We found that this hybrid peptide had cytotoxic activity against NRP1-positive pancreatic cancer cell lines such as BxPC-3 and Panc-1, whereas the peptide did not affect the viability of normal cells in vitro. It was also found by affinity analysis that Sema3A peptide binds to NRP1, and two arginines (372R and 377R) in Sema3A peptide are involved in the interaction with NRP1 protein. In addition, confocal microscopy analysis revealed that Sema3A-lytic peptide could not penetrate normal cells regardless of the presence of NRP1 mRNA, suggesting that the ability of Sema3A-lytic peptide to concentrate adjacent to the cell membrane by binding to NRP1 with the target-binding moiety contributes to its selective cytotoxic activity. These results indicate that Sema3A-lytic hybrid peptide would be a possible anti-cancer agent for treatment of human pancreatic cancer. 相似文献
175.
Chiharu Sadakane Shuichi Muto Koji Nakagawa Shunsuke Ohnishi Yayoi Saegusa Miwa Nahata Tomohisa Hattori Masahiro Asaka Hiroshi Takeda 《Biochemical and biophysical research communications》2011,(3):506
Rikkunshito (RKT), a Japanese traditional medicine, has been shown to stimulate food intake in rats with cisplatin-induced anorexia; however, the underlying mechanisms remain unknown. In this study, we investigated whether RKT is involved in the degradation of peripheral ghrelin. RKT inhibited decreases in plasma ghrelin level and enhanced acyl- to desacyl-ghrelin (A/D) ratio in cisplatin-treated rats. Several components of RKT demonstrated inhibitory activity against ghrelin deacylating enzymes. In addition, 10-gingerol, a component of RKT, inhibited exogenous ghrelin deacylation. Therefore, RKT may enhance plasma acyl-ghrelin level, at least in part, by inhibiting the circulating ghrelin degrading enzyme. 相似文献
176.
Hideshi Yanase Tomohisa Kotani Kenzo Tonomura 《Bioscience, biotechnology, and biochemistry》2013,77(12):3139-3144
A method for the transformation of Zymomonas mobilis with plasmid DNA was developed by using shuttle vectors, pZA31, pZA32 and pZA33, as a source of transforming DNA. Partial spheroplasts of Z. mobilis were prepared by growing cells in a hypertonic medium supplemented with a drug which inhibits the biosynthesis of bacterial cell walls, such as penicillin G and d-cycloserine. They were transformed with plasmid DNA in the presence of 15% polyethylene glycol 6,000, after treated with 100 mm CaCl2. The frequency of transformation obtained was 104 to 105 transformants/μg of DNA for Z. mobilis IFO13756 (Z-6). 相似文献
177.
Tomohisa Moriguchi Mitsuaki Sekine Kazuo Shinozuka 《Bioorganic & medicinal chemistry》2013,21(24):8013-8018
Efficient synthesis of a dithymidine dinucleotide analog bearing a diisopropylsilyl linkage instead of a phosphodiester linkage is described with respect to its incorporation into oligonucleotides. The diisopropylsilyl linkage was introduced into the oligonucleotide by preparation of the phosphoramidite derivative of a dithymidine dimer unit. The diisopropylsilyl-modified oligonucleotide exhibited hybridization behavior with both single strand and duplex DNA. The thermal stability of both the duplex and triplex showed a relative instability compared to the corresponding natural phosphodiester DNA, because of the steric hindrance of the isopropyl group on the silicon atom. 相似文献
178.
179.
A mechanism of the C―S bond activation of S-adenosylmethionine (SAM) in biotin synthase is discussed from quantum mechanical/molecular mechanical (QM/MM) computations. The active site of the enzyme involves a [4Fe-4S] cluster, which is coordinated to the COO− and NH2 groups of the methionine moiety of SAM. The unpaired electrons on the iron atoms of the [4Fe-4S]2+ cluster are antiferromagnetically coupled, resulting in the S = 0 ground spin state. An electron is transferred from an electron donor to the [4Fe-4S]2+-SAM complex to produce the catalytically active [4Fe-4S]+ state. The SOMO of the [4Fe-4S]+-SAM complex is localized on the [4Fe-4S] moiety and the spin density of the [4Fe-4S] core is calculated to be 0.83. The C―S bond cleavage is associated with the electron transfer from the [4Fe-4S]+ cluster to the antibonding σ* C―S orbital. The electron donor and acceptor states are effectively coupled with each other at the transition state for the C―S bond cleavage. The activation barrier is calculated to be 16.0 kcal/mol at the QM (B3LYP/SV(P))/MM (CHARMm) level of theory and the C―S bond activation process is 17.4 kcal/mol exothermic, which is in good agreement with the experimental observation that the C―S bond is irreversibly cleaved in biotin synthase. The sulfur atom of the produced methionine molecule is unlikely to bind to an iron atom of the [4Fe-4S]2+ cluster after the C―S bond cleavage from the energetical and structural points of view. 相似文献
180.
Glutamate dehydrogenase (GDH) catalyzes reversible conversion between glutamate and 2-oxoglutarate using NAD(P)(H) as a coenzyme. Although mammalian GDH is regulated by GTP through the antenna domain, little is known about the mechanism of allosteric activation by leucine. An extremely thermophilic bacterium, Thermus thermophilus, possesses GDH with a unique subunit configuration composed of two different subunits, GdhA (regulatory subunit) and GdhB (catalytic subunit). T. thermophilus GDH is unique in that the enzyme is subject to allosteric activation by leucine. To elucidate the structural basis for leucine-induced allosteric activation of GDH, we determined the crystal structures of the GdhB-Glu and GdhA-GdhB-Leu complexes at 2.1 and 2.6 Å resolution, respectively. The GdhB-Glu complex is a hexamer that binds 12 glutamate molecules: six molecules are bound at the substrate-binding sites, and the remaining six are bound at subunit interfaces, each composed of three subunits. The GdhA-GdhB-Leu complex is crystallized as a heterohexamer composed of four GdhA subunits and two GdhB subunits. In this complex, six leucine molecules are bound at subunit interfaces identified as glutamate-binding sites in the GdhB-Glu complex. Consistent with the structure, replacement of the amino acid residues of T. thermophilus GDH responsible for leucine binding made T. thermophilus GDH insensitive to leucine. Equivalent amino acid replacement caused a similar loss of sensitivity to leucine in human GDH2, suggesting that human GDH2 also uses the same allosteric site for regulation by leucine. 相似文献