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Shinya Honda

Publications and source records attributed to Shinya Honda.

8 recordsLinked to original sources
PubMed2006

Structural diversity of protein segments follows a power-law distribution.

The local structures of protein segments were classified and their distribution was analyzed to explore the structural diversity of proteins. Representative proteins were divided into short segments using a sliding L-residue window. Each set of local structures consisting of consecutive 1-31 amino acids was classified using a single-pass clustering method. The results demonstrate that the local structures of proteins are very unevenly distributed in the protein universe. The distribution of local structures of relatively long segments shows a power-law behavior that is formulated well by Zipf's law, implying that a protein structure possesses recursive and fractal characteristics. The degree of effective conformational freedom per residue as well as the structure entropy per residue decreases gradually with an increasing value of L and then converges to constant values. This suggests that the number of protein conformations resides within the range between 1.2L and 1.5L and that 10- to 20-residue segments are already proteinlike in terms of their structural diversity.

Amino Acid Motifs↗
PubMed2005

Molecular characterization of mitocalcin, a novel mitochondrial Ca2+-binding protein with EF-hand and coiled-coil domains.

Here we have identified and characterized a novel mitochondrial Ca2+-binding protein, mitocalcin. Western blot analysis demonstrated that mitocalcin was widely expressed in mouse tissues. The expression in brain was increased during post-natal to adult development. Further analyses were carried out in newly established neural cell lines. The protein was expressed specifically in neurons but not in glial cells. Double-labeling studies revealed that mitocalcin was colocalized with mitochondria in neurons differentiated from 2Y-3t cells. In addition, mitocalcin was enriched in the mitochondrial fraction purified from the cells. Immunohistochemical studies on mouse cerebellum revealed that the expression pattern of mitocalcin in glomeruli of the internal granular and molecular layers was well overlapped by the distribution pattern of mitochondria. Immunogold electron microscopy showed that mitocalcin was associated with mitochondrial inner membrane. Overexpression of mitocalcin in 2Y-3t cells resulted in neurite extension. Inhibition of the expression in 2Y-3t cells caused suppression of neurite outgrowth and then cell death. These findings suggest that mitocalcin may play roles in neuronal differentiation and function through the control of mitochondrial function.

Amino Acid Sequence↗
PubMed2005

Higher-order molecular packing in amyloid-like fibrils constructed with linear arrangements of hydrophobic and hydrogen-bonding side-chains.

Various mutants of the protein fragment, barnase module-1 (1-24) were investigated in order to reveal the structural principle of amyloid-like fibrils. By means of circular dichroism spectroscopy, X-ray diffraction, electron microscopy, and thioflavin T binding assay, we found that the molecules containing two beta-strands and an intervening turn structure are assembled to form a cross-beta structure. Stabilization by both the hydrophobic interactions and hydrogen bonding between the respective paired side-chains on the coupled beta-strands was essential for fibril formation. These two types of interaction can also arrange the corresponding residues in lines on both sheet surfaces of protofilaments with a cross-beta structure. This leads to the most probable fibril structure constructed with the line-matching interactions between protofilaments. Consideration of the geometrical symmetry resulted in our finding that a limited number of essential models for molecular packing in fibril structure are stable, which would rationally explain the occurrence of two or three morphologies from an identical molecular species. The ribbon-like fibrils exhibited striped texture along the axis, which was assigned to a stacked two-sheet repeat as a structural unit. The comprehensively proposed structural model, that is, the sheet-sheet interaction between left-handed cross-beta structures, results in a slightly right-handed twist of beta-sheet stacking, which reasonably elucidates the intrinsic sizes of the fibril width and its helical period along the fibril axis, as the bias in the orientation of the hydrogen-bonded beta-strand pair at the lateral edge is larger than that at the central protofilament.

Amyloid↗
PubMed2005

Effects of exogenous big endothelin-1 on regional blood flow in fetal lambs.

OBJECTIVE: Endothelin-1, a 21 amino acid polypeptide produced by vascular endothelial cells, has potent vasoactive properties. The purpose of this study was to estimate the effects of exogenous big endothelin-1 on fetal lamb circulation. METHODS: Regional blood flow was measured by the colored microsphere technique during continuous infusion (60 minutes) of big endothelin-1, or saline (control), in 12 chronically instrumented sheep fetuses. RESULTS: After 60 minutes of big endothelin-1 administration, the fetal plasma endothelin-1 concentration increased significantly from 24.0 +/- 6.7 to 49.7 +/- 31.4 pg/mL (P = .018) without significant changes in fetal arterial blood gases. Continuous infusion of big endothelin-1 decreased blood flow in most organs except the brain and the heart. After the big endothelin-1 infusion, the blood flow to the brain significantly increased from 158 +/- 51 to 174 +/- 71 mL/min/100 g (P = .002); the blood flow to the heart also increased significantly from 171 +/- 95 to 200 +/- 112 mL/min/100 g (P = .001), respectively. CONCLUSION: Continuous infusion of endothelin-1 decreases blood flow in most of organs except the brain and the heart. It is likely that endothelin-1 plays an important role in fetal redistribution of blood flow.

Animals↗
PubMed2005

A bipotent neural progenitor cell line cloned from a cerebellum of an adult p53-deficient mouse generates both neurons and oligodendrocytes.

Here we report developmental characteristics of a clonal cell line 2Y-3t established from a multifocal neoplasm that arose in a cerebellum of an adult p53-deficient mouse. The tumorigenicity of the line was not observed in soft agar assay or in nude mouse assay. In serum-containing medium, 2Y-3t cells were epithelial-like in morphology and were mitotic. When they were cultured in serum-free medium, the expressions of neural stem and/or progenitor cell markers were decreased. Concomitantly, the expressions of neuronal and oligodendrocyte markers were increased in concert with morphological differentiation, and DNA synthesis ceased. None of astrocyte markers were detected under these culture conditions. Double-labelling studies revealed that two cell populations coexisted, expressing neuronal or oligodendrocyte markers. Triiodothyronine (T3) increased the oligodendrocyte population when 2Y-3t cells were cultured in serum-free medium. Recloning of the line gave rise to three types of subclones. Sixteen subclones were capable of generating both neurons and oligodendrocytes, four subclones were capable of generating only neurons and one subclone was capable of generating only oligodendrocytes. Thus, 2Y-3t cells have characteristics of bipotent neural progenitor cells capable of generating both neurons and oligodendrocytes. In addition, the line expressed mRNA for Pax-2 and had GAD67-positive cells when cultured in serum-free medium. However, none of the mRNAs for Zic-1, Math1, zebrin or Calbindin-D28k were detected, suggesting that the 2Y-3t line might generate the GABAergic interneuron lineage of the mouse cerebellum.

Animals↗
PubMed2004

10 residue folded peptide designed by segment statistics.

We have designed a peptide termed chignolin, consisting of only 10 amino acid residues (GYDPETGTWG), on the basis of statistics derived from more than 10,000 protein segments. The peptide folds into a unique structure in water and shows a cooperative thermal transition, both of which may be hallmarks of a protein. Also, the experimentally determined beta-hairpin structure was very close to what we had targeted. The performance of the short peptide not only implies that the methodology employed here can contribute toward development of novel techniques for protein design, but it also yields insights into the raison d'etre of an autonomous element involved in a natural protein. This is of interest for the pursuit of folding mechanisms and evolutionary processes of proteins.

Algorithms↗
PubMed2004

Effects of nitric oxide and prostacyclin on hemodynamic response by big endothelin-1 in near term fetal sheep.

AIMS: To measure plasma concentrations of endothelin (ET)-1, NO metabolites (nitrate/nitrite; NOx) and 6-keto PGF1 alpha (PGF1 alpha) in maternal and fetal sheep blood, and to evaluate the effects of big ET-1 on hemodynamic response, blood gases and NO and 6-keto PGF1 alpha production in near term fetal sheep. METHODS: Hemodynamic parameters were measured during infusion of big ET-1 into the carotid vein in chronically catheterized fetal sheep on day 125 of gestation. Fetal arterial blood samples were obtained for ET-1, PGF1 alpha) and nitrate/nitrite (NOx) measurements. RESULTS: ET-1, NOx and PGF1 alpha plasma concentrations were all significantly higher in fetal compared with the maternal plasma. Big ET-1 significantly decreased fetal systolic and diastolic blood pressure and significantly increased fetal heart rate. Big ET-1 stimulated plasma PGF1 alpha), but not NOx , concentration. CONCLUSIONS: Circulatory regulating factors in the fetus were up-regulated. The effects of ET-1 on fetal hemodynamic response may be mediated via prostacyclin, but not via the NO pathway.

Animals↗