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Biomedical subjects

Yuki Kimura

Publications and source records attributed to Yuki Kimura.

11 recordsLinked to original sources
PubMed2006

Hypochlorous acid-derived modification of phospholipids: characterization of aminophospholipids as regulatory molecules for lipid peroxidation.

Hypochlorous acid (HOCl), an inflammatory oxidant derived from neutrophil myeloperoxidase, can chlorinate cytosolic proteins and nuclear DNA bases of target cells by passing through the cell membrane. However, little is known about the consequences of HOCl-derived modification of cell membrane components, including phospholipids. In this study, we characterize the reaction of HOCl with phospholipid molecules and found that aminophospholipids are the key molecules that chemically regulate lipid peroxidation. Upon incubation with HOCl, the peroxidation of egg yolk phosphatidylcholine was significantly enhanced in the presence of phosphatidylethanolamine (PE). In contrast, the peroxidation was significantly inhibited in the presence of phosphatidylserine (PS). On the basis of mass spectrometric and electron paramagnetic resonance characterization, the initiator of the peroxidation was identified as the nitrogen-centered radical originating from PE-derived chloramines, especially N,N-dichlorinated PE, a major product in the HOCl-modified PE. Although PS was also chlorinated upon reaction with HOCl, the formed chloramine rapidly decomposed to phosphatidylglycolaldehyde, a novel class of lipid aldehyde. Formation of phosphatidylglycolaldehyde was also confirmed in the porcine brain PS and erythrocyte cell membrane ghost exposed to HOCl. These results provide a novel mechanism for the HOCl-induced oxidative damage and its endogenous protection in the cell membrane at the site of inflammation.

Chromatography, High Pressure Liquid↗
PubMed2006

fRNAdb: a platform for mining/annotating functional RNA candidates from non-coding RNA sequences.

There are abundance of transcripts that code for no particular protein and that remain functionally uncharacterized. Some of these transcripts may have novel functions while others might be junk transcripts. Unfortunately, the experimental validation of such transcripts to find functional non-coding RNA candidates is very costly. Therefore, our primary interest is to computationally mine candidate functional transcripts from a pool of uncharacterized transcripts. We introduce fRNAdb: a novel database service that hosts a large collection of non-coding transcripts including annotated/non-annotated sequences from the H-inv database, NONCODE and RNAdb. A set of computational analyses have been performed on the included sequences. These analyses include RNA secondary structure motif discovery, EST support evaluation, cis-regulatory element search, protein homology search, etc. fRNAdb provides an efficient interface to help users filter out particular transcripts under their own criteria to sort out functional RNA candidates. fRNAdb is available at http://www.ncrna.org/

Base Sequence↗
PubMed2005

Hzf protein regulates dendritic localization and BDNF-induced translation of type 1 inositol 1,4,5-trisphosphate receptor mRNA.

The localization of certain mRNAs to dendrites and their local translation in synaptic regions are proposed to be involved in certain aspects of synaptic plasticity. A cis-acting element within the 3' untranslated region (3' UTR) of the targeted mRNAs, which is bound by a trans-acting RNA-binding protein, controls the dendritic mRNA localization. Here, we identified hematopoietic zinc finger (Hzf) as a trans-acting factor that regulates the dendritic mRNA localization of the type 1 inositol 1,4,5-trisphosphate receptor (IP(3)RI), a dendritically localized mRNA in cerebellar Purkinje cells, via binding to the 3' UTR. In Hzf-deficient mice, the dendritic localization of IP(3)RI mRNA and brain-derived neurotrophic factor-induced IP(3)RI protein synthesis in the cerebellum were impaired. These findings suggest that Hzf is an RNA-binding protein that controls the dendritic mRNA localization and activity-dependent translation of IP(3)RI, and may be involved in some aspects of synaptic plasticity.

3' Untranslated Regions↗
PubMed2004

Targeted mutations of the juxtamembrane tyrosines in the Kit receptor tyrosine kinase selectively affect multiple cell lineages.

Loss-of-function mutations in the murine dominant white spotting/c-kit locus affect a diverse array of biological processes and cell lineages and cause a range of phenotypes, including severe anemia, defective pigmentation, sterility, mast cell deficits, a lack of interstitial cells of Cajal, spatial learning memory deficits, and defects in peripheral nerve regeneration. Here we show that tyrosine residues 567 and 569 in the juxtamembrane (Jx) domain of the murine Kit receptor tyrosine kinase are crucial for the function of Kit in melanogenesis and mast cell development, but are dispensable for the normal development of erythroid, interstitial cells of Cajal and germ cells. Furthermore, adult mice lacking both tyrosines exhibit splenomegaly, dysregulation of B-cell and megakaryocyte development, and enlarged stomachs. Analysis of signal transduction events induced by the mutant receptors after ligand stimulation indicates that Jx tyrosine mutations diminish receptor autophosphorylation and selectively attenuate activation of extracellular signal-regulated kinase/mitogen-activated protein kinases. Together, these observations demonstrate that the Jx domain of Kit plays a cell-type specific regulatory role in vivo and illustrate how engineered mutations in Kit can be used to understand the complex biological and molecular events that result from activating a receptor tyrosine kinase.

Animals↗
PubMed2003

Reduction of paraquat-induced oxidative stress in rats by dietary soy peptide.

The effect of a dietary soy protein isolate (SPI), soy peptide (PEP) and the amino acids in soy protein on paraquat (PQ)-induced oxidative stress was investigated in rats. In the first experiment, male Wistar rats were fed on experimental diets containing casein (CAS), SPI and PEP as nitrogen sources with or without 0.025% PQ. The reduced food intake and body weight gain of the rats fed with PQ was mitigated by either the SPI or PEP intake. Both SPI and PEP prevented the elevation of the serum TBARS concentration and tended to prevent the elevation of lung weight induced by PQ. In the second experiment, the rats were fed on diets containing an amino acid mixture resembling casein (CASAA) or soy protein (SPIAA) with or without PQ. The SPIAA intake did not affect the reduction of food intake and body weight gain, nor the elevation of lung weight and TBARS in the serum and liver induced by PQ. These results demonstrate that the intake of either dietary SPI or PEP, but not an amino acid mixture resembling soy protein, had the effect of reducing PQ-induced oxidative stress in rats.

Amino Acids↗
PubMed2002

Zinc finger protein, Hzf, is required for megakaryocyte development and hemostasis.

Using an expression gene trapping strategy, we recently identified a novel gene, hematopoietic zinc finger (Hzf), which encodes a protein containing three C(2)H(2)-type zinc fingers that is predominantly expressed in megakaryocytes. Here, we have examined the in vivo function of Hzf by gene targeting and demonstrated that Hzf is essential for megakaryopoiesis and hemostasis in vivo. Hzf-deficient mice exhibited a pronounced tendency to rebleed and had reduced alpha-granule substances in both megakaryocytes and platelets. These mice also had large, faintly stained platelets, whereas the numbers of both megakaryocytes and platelets were normal. These results indicate that Hzf plays important roles in regulating the synthesis of alpha-granule substances and/or their packing into alpha-granules during the process of megakaryopoiesis.

Animals↗
PubMed2002

Examining time trends in the Oldowan technology at Beds I and II, Olduvai Gorge.

The lithic analysis of the Bed I and II assemblages from Olduvai Gorge reveals both static and dynamic time trends in early hominids' technology from 1.8 to 1.2 m.y.a. The Bed I Oldowan (1.87-1.75 m.y.a.) is characterized by the least effort strategy in terms of raw material exploitation and tool production. The inclusion of new raw material, chert, for toolmaking in the following Developed Oldowan A (DOA, 1.65-1.53 m.y.a.) facilitated more distinctive and variable flaking strategies depending on the kind of raw materials. The unique characters of DOA are explainable by this raw material factor, rather than technological development of hominids. The disappearance of chert in the subsequent Developed Oldowan B and Acheulian (1.53-1.2 m.y.a.) necessitated a shift in tool production strategy more similar to that of Bed I Oldowan than DOA. However, the evidence suggests that Bed II hominids might have been more skillful toolmakers, intensive tool-users, and engaged in more active transport of stone tools than the Bed I predecessors. Koobi Fora hominids maintained a more static tool-using behavior than their Olduvai counterparts due mainly to a stable supply of raw materials. They differed from Olduvai hominids in terms of less battering of cores, consistent transport behavior, and few productions of side-struck flakes, indicating a regional variation of toolmaking and using practice. However, they shared with Olduvai hominids a temporal trend toward the production of larger flakes from larger cores after 1.6 m.y.a. Increased intake of animal resources and the expansion of ranging area of Homo ergaster would have led to the development of technological organization. Technological changes in the Oldowan industry are attested at Olduvai Gorge, Koobi Fora, and Sterkfontein, suggesting that it was a pan-African synchronous phenomenon, beginning at 1.5 m.y.a.

Animals↗
PubMed2002

Evaluation of carcinogenic/co-carcinogenic activity of chikusaku-eki, a bamboo charcoal by-product used as a folk remedy, in BALB/c 3T3 cells.

Chikusaku-eki is an acidic dark brown liquid obtained as a by-product from bamboo charcoal burners. The solution diluted with water is gaining widespread popularity in Japan as a folk medicine for skin diseases such as scabies, eczema, and atopic dermatitis. In this study, the carcinogenic and tumor-promoting potential of chikusaku-eki was determined using the BALB/c 3T3 A31-1-1 cell transformation system. Carcinogenic activity was tested by treating A31-1-1 cells for 24 h with 0.06% solution, a dose resulting in 35% clonogenic cell survival. In both 2-O-tetradecanoylphorbol-13-acetate (TPA)-treated and non-treated groups, chikusaku-eki did not initiate carsinogenesis. Following initiation with 3-methylcholanthrene (3-MCA), A31-1-1 cells were chronically treated with a non-toxic concentration range of chikusaku-eki (< or = 0.01%), but chikusaku-eki did not act as a tumor promoter. Thus, chikusaku-eki was not carcinogenic/co-carcinogenic in the in vitro cell transformation assay examined in this study after being diluted more than 10(4)-fold with water.

3T3 Cells↗