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81.
82.
Yasuhiro Moriwaki Kiyoko Takada Toshinori Nagasaki Natsuki Kubo Tomohiro Ishii Kazuaki Kose Taihei Kageyama Shoutaro Tsuji Koichiro Kawashima Hidemi Misawa 《PloS one》2015,10(10)
Background
SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Moreover, although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied, and the pathophysiological control of SLURP1 expression in keratinocytes is largely unknown.Objectives
Our aim was to examine the involvement of SLURP1 in the pathophysiology of psoriasis using an imiquimod (IMQ)-induced psoriasis model mice and normal human epidermal keratinocytes (NHEKs).Results
SLURP1 expression was up-regulated in the skin of IMQ-induced psoriasis model mice. In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-α, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines. The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3. Because IL-22 induces production of antimicrobial proteins in epithelial cells, the antibacterial activity of SLURP1 was assessed against Staphylococcus aureus (S. aureus), which is known to be associated with disease severity in psoriasis. SLURP1 significantly suppressed the growth of S. aureus.Conclusions
These results indicate SLURP1 participates in pathophysiology of psoriasis by regulating keratinocyte proliferation and differentiation, and by suppressing the growth of S. aureus. 相似文献83.
Hiroyuki Imai Kiyoshi Kano Wataru Fujii Ken Takasawa Shoichi Wakitani Masato Hiyama Koichiro Nishino Ken Takeshi Kusakabe Yasuo Kiso 《PloS one》2015,10(6)
Polyploid amphibians and fishes occur naturally in nature, while polyploid mammals do not. For example, tetraploid mouse embryos normally develop into blastocysts, but exhibit abnormalities and die soon after implantation. Thus, polyploidization is thought to be harmful during early mammalian development. However, the mechanisms through which polyploidization disrupts development are still poorly understood. In this study, we aimed to elucidate how genome duplication affects early mammalian development. To this end, we established tetraploid embryonic stem cells (TESCs) produced from the inner cell masses of tetraploid blastocysts using electrofusion of two-cell embryos in mice and studied the developmental potential of TESCs. We demonstrated that TESCs possessed essential pluripotency and differentiation potency to form teratomas, which differentiated into the three germ layers, including diploid embryonic stem cells. TESCs also contributed to the inner cell masses in aggregated chimeric blastocysts, despite the observation that tetraploid embryos fail in normal development soon after implantation in mice. In TESCs, stability after several passages, colony morphology, and alkaline phosphatase activity were similar to those of diploid ESCs. TESCs also exhibited sufficient expression and localization of pluripotent markers and retained the normal epigenetic status of relevant reprogramming factors. TESCs proliferated at a slower rate than ESCs, indicating that the difference in genomic dosage was responsible for the different growth rates. Thus, our findings suggested that mouse ESCs maintained intrinsic pluripotency and differentiation potential despite tetraploidization, providing insights into our understanding of developmental elimination in polyploid mammals. 相似文献
84.
Michio Nakamura Hitoshige Hayaki Kazuhiko Hosaka Noriko Itoh Koichiro Zamma 《American journal of physical anthropology》2014,153(1):139-143
If a social‐living animal has a long life span, permitting different generations to co‐exist within a social group, as is the case in many primate species, it can be beneficial for a parent to continue to support its weaned offspring to increase the latter's survival and/or reproductive success. Chimpanzees have an even longer period of dependence on their mothers' milk than do humans, and consequently, offspring younger than 4.5–5 years old cannot survive if the mother dies. Most direct maternal investments, such as maternal transportation of infants and sharing of night shelters (beds or nests), end with nutritional weaning. Thus, it had been assumed that a mother's death was no longer critical to the survival of weaned offspring, in contrast to human children, who continue to depend on parental care long after weaning. However, in theory at least, maternal investment in a chimpanzee son after weaning could be beneficial because in chimpanzees' male‐philopatric society, mother and son co‐exist for a long time after the offspring's weaning. Using long‐term demographic data for a wild chimpanzee population in the Mahale Mountains, Tanzania, we show the first empirical evidence that orphaned chimpanzee sons die younger than expected even if they lose their mothers after weaning. This suggests that long‐lasting, but indirect, maternal investment in sons continues several years after weaning and is vital to the survival of the sons. The maternal influence on males in the male‐philopatric societies of hominids may be greater than previously believed. Am J Phys Anthropol, 153:139–143, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
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86.
The mechanism of increasing effect of CuCl2 on specific [3H]cimetidine binding was examined in brain membranes of rats. CuCl2-Induced elevation of [3H]cimetidine binding was high in Krebs-Ringer solution (pH 7.4) compared to those in 50 mM Na, K-phosphate buffer (pH 7.4) and in 50 mM Tris-HCl buffer (pH 7.4). CaCl2 (5–50 mM) inhibited effect of CuCl2, but NaCl (25–200 mM), KCl (5–100 mM) or MgCl2 (5–50 mM) did not. CuCl2 (50 μM) elevated 9.3- and 2.5-fold the binding in phosphate- and Tris—HCl buffer, respectively. EDTA-2Na decreased the binding elevated by 50 μM CuCl2 in phosphate buffer to the similar level in Tris-HCl buffer, whereas it did not affect those in Tris-HCl buffer. The absorption spectra of cimetidine and CuCl2 mixture showed a peak at 317 nm in phosphate buffer that was not observed in Tris-HCl buffer. It is suggested that cimetidine-Cu2+ chelate complex could be formed in phosphate buffer, resulting in higher amount of binding in phosphate buffer than in Tris-HCl buffer. PdCl2 also caused a marked elevation in [3H]cimetidine binding, seeming to be due to formation of cimetidine-Pd2+ chelate complex. There were two types of [3H]cimetidine binding in the presence of 20 nM PdCl2: high affinity binding with Kd = 0.7 ± 0.1 nM and low affinity binding with Kd = 44.3 ± 3.0 nM. It is suggested that cimetidine-Cu2+ complex binds to cimetidine binding sites in brain with higher affinity than cimetidine alone. 相似文献
87.
A novel mutated acetolactate synthase gene conferring specific resistance to pyrimidinyl carboxy herbicides in rice 总被引:3,自引:0,他引:3
Acetolactate synthase (ALS) is the first common enzyme in the biosynthetic pathway of branched-chain amino acids. Mutations
of specific amino acids in ALS have been known to confer resistance to ALS-inhibiting herbicides such as sulfonylureas and
pyrimidinyl carboxy (PC) herbicides. However, mutations conferring exclusive resistance to PC have not yet been reported to
date. We selected PC resistant rice calli, which were derived from anther culture, using one of the PCs, bispyribac-sodium
(BS), as a selection agent. Two lines of BS-resistant plants carrying a novel mutation, the 95th Glycine to Alanine (G95A),
in ALS were obtained. In vitro ALS activity assay indicated that the recombinant protein of G95A-mutated ALS (ALS-G95A) conferred
highly specific resistance to PC herbicides. In order to determine if the ALS-G95A gene could be used as a selection marker
for rice transformation, the ALS-G95A gene was connected to ubiquitin promoter and introduced into rice. PC resistant plants
containing integrated ALS-G95A gene were obtained after selection with BS as a selection agent. In conclusion, novel G95A
mutated ALS gene confers highly specific resistant to PC-herbicides and can be used as a selection marker. 相似文献
88.
Sugiura H Liu X Togo S Kobayashi T Shen L Kawasaki S Kamio K Wang XQ Mao LJ Rennard SI 《Journal of cellular physiology》2007,210(1):99-110
Prostaglandin E(2) (PGE(2)) has been shown to have a strong cytoprotective effect, inhibiting apoptosis. In the present study, we evaluated whether PGE(2) has a protective effect on cigarette smoke extract (CSE)-induced apoptosis in human lung fibroblasts. Apoptosis was assessed by various methods, including DNA content analysis. CSE (15%-20%) led to apoptosis and induced imbalance in favor of pro- over anti-apoptotic protein expression and activated caspases. PGE(2) blocked CSE-induced apoptosis and modulated the balance of pro- and anti-apoptotic proteins and decreased the activation of caspases. This anti-apoptotic effect was mediated via EP(2) receptor activation as the EP(2) agonist butaprost mimicked PGE(2) activity and siRNA for the EP(2) receptor blocked it. An adenylyl cyclase inhibitor was found to abolish the PGE(2)-mediated cytoprotective effect. Correspondingly, c-AMP analogs blocked CSE-induced apoptosis. Consistently, the protein kinase A (PKA) inhibitor KT-5720 abolished PGE(2)-mediated protection. PGE(2) and butaprost phosphorylated Bad and KT-5720 blocked phosphorylation. These results suggest that PGE(2) inhibits CSE-induced apoptosis via EP(2) receptor activation and activation of PKA, which leads to an alteration in the balance between pro- and anti-apoptotic factors. Through such a mechanism, PGE(2) may alter survival of cells in the smoke-exposed lungs, thus affecting the pathogenesis of cigarette smoke-induced disease. 相似文献
89.
Molecular basis of guanine nucleotide dissociation inhibitor activity of human neuroglobin by chemical cross-linking and mass spectrometry 总被引:1,自引:0,他引:1
Kitatsuji C Kurogochi M Nishimura S Ishimori K Wakasugi K 《Journal of molecular biology》2007,368(1):150-160
Oxidized human neuroglobin (Ngb), a heme protein expressed in the brain, has been proposed to act as a guanine nucleotide dissociation inhibitor (GDI) for the GDP-bound form of the heterotrimeric G protein alpha-subunit (Galpha(i)). Here, to elucidate the molecular mechanism underlying the GDI activity of Ngb, we used an glutathione-S-transferase pull-down assay to confirm that Ngb competes with G-protein betagamma-subunits (Gbetagamma) for binding to Galpha(i), and identified the Galpha(i)-binding site in Ngb by chemical cross-linking with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and sulfo-N-hydroxysuccinimide, coupled with mass spectrometry (MS). Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis for tryptic peptides derived from the cross-linked Ngb-Galpha(i) complex revealed several binding regions in Ngb. Furthermore, MALDI-TOF/TOF MS analysis of the cross-linked Ngb and Galpha(i) peptides, together with the MS/MS scoring method, predicted cross-linking between Glu60 (Ngb) and Ser206 (Galpha(i)), and between Glu53 (Ngb) and Ser44 (Galpha(i)). Because Ser206 of Galpha(i) is located in the region that contacts Gbetagamma, binding of Ngb could facilitate the release of Gbetagamma from Galpha(i). Binding of Ngb to Galpha(i) would also inhibit the exchange of GDP for GTP, because Ser44 (Galpha(i)) is adjacent to the GDP-binding site and Glu53 (Ngb), which is cross-linked to Ser44 (Galpha(i)), could be located close to GDP. Thus, we have identified, for the first time, the sites of interaction between Ngb and Galpha(i), enabling us to discuss the functional significance of this binding on the GDI activity of Ngb. 相似文献
90.