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51.
Satoshi Serada Atsushi Tanemura Fei Yang Shintaro Nomura Akira Kudo Kenji Izuhara Hiroyuki Murota Minoru Fujimoto Ichiro Katayama Tetsuji Naka 《Pigment cell & melanoma research》2014,27(4):630-639
Given no reliable therapy for advanced malignant melanoma, it is important to elucidate the molecular mechanisms underlying the disease progression. Using a quantitative proteomics approach, the ‘isobaric tags for relative and absolute quantitation (iTRAQ)’ method, we identified that the extracellular matrix protein, periostin (POSTN), was highly expressed in invasive melanoma compared with normal skin. An immunohistochemical analysis showed that POSTN was expressed in all invasive melanoma (n = 20) and metastatic lymph node (n = 5) tissue samples, notably restricted in their stroma. In terms of the intercellular regulation of POSTN, we found that there was upregulation of POSTN when melanoma cells and normal human dermal fibroblasts (NHDFs) were cocultured, with restricted expression of TGF‐β1 and TGF‐β3. In a functional analyses, recombinant and NHDF‐derived POSTN significantly accelerated melanoma cell proliferation via the integrin/mitogen‐activated protein kinase (MAPK) signaling pathway in vitro. The size of implanted melanoma tumors was significantly suppressed in POSTN/Rag2 double knockout mice compared with Rag2 knock‐out mice. These results indicate that NHDF‐derived POSTN accelerates melanoma progression and might be a promising therapeutic target for malignant melanoma. 相似文献
52.
Akemi Shodai Toshifumi Morimura Akemi Ido Tsukasa Uchida Takashi Ayaki Rina Takahashi Soichiro Kitazawa Sakura Suzuki Mikako Shirouzu Takanori Kigawa Yutaka Muto Shigeyuki Yokoyama Ryosuke Takahashi Ryo Kitahara Hidefumi Ito Noriko Fujiwara Makoto Urushitani 《The Journal of biological chemistry》2013,288(21):14886-14905
Aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is a pathological signature of amyotrophic lateral sclerosis (ALS). Although accumulating evidence suggests the involvement of RNA recognition motifs (RRMs) in TDP-43 proteinopathy, it remains unclear how native TDP-43 is converted to pathogenic forms. To elucidate the role of homeostasis of RRM1 structure in ALS pathogenesis, conformations of RRM1 under high pressure were monitored by NMR. We first found that RRM1 was prone to aggregation and had three regions showing stable chemical shifts during misfolding. Moreover, mass spectrometric analysis of aggregated RRM1 revealed that one of the regions was located on protease-resistant β-strands containing two cysteines (Cys-173 and Cys-175), indicating that this region served as a core assembly interface in RRM1 aggregation. Although a fraction of RRM1 aggregates comprised disulfide-bonded oligomers, the substitution of cysteine(s) to serine(s) (C/S) resulted in unexpected acceleration of amyloid fibrils of RRM1 and disulfide-independent aggregate formation of full-length TDP-43. Notably, TDP-43 aggregates with RRM1-C/S required the C terminus, and replicated cytopathologies of ALS, including mislocalization, impaired RNA splicing, ubiquitination, phosphorylation, and motor neuron toxicity. Furthermore, RRM1-C/S accentuated inclusions of familial ALS-linked TDP-43 mutants in the C terminus. The relevance of RRM1-C/S-induced TDP-43 aggregates in ALS pathogenesis was verified by immunolabeling of inclusions of ALS patients and cultured cells overexpressing the RRM1-C/S TDP-43 with antibody targeting misfolding-relevant regions. Our results indicate that cysteines in RRM1 crucially govern the conformation of TDP-43, and aberrant self-assembly of RRM1 at amyloidogenic regions contributes to pathogenic conversion of TDP-43 in ALS. 相似文献
53.
Histone modifications are associated with meiotic recombination hotspots, discrete sites with augmented recombination frequency. For example, trimethylation of histone H3 lysine4 (H3K4me3) marks most hotspots in budding yeast and mouse. Modified histones are known to regulate meiotic recombination partly by promoting DNA double-strand break (DSB) formation at hotspots, but the role and precise landscape of involved modifications remain unclear. Here, we studied hotspot-associated modifications in fission yeast and found general features: acetylation of H3 lysine9 (H3K9ac) is elevated, and H3K4me3 is not significantly enriched. Mutating H3K9 to non-acetylatable alanine mildly reduced levels of the DSB-inducing protein Rec12 (the fission yeast homologue of Spo11) and DSB at hotspots, indicating that H3K9ac may be involved in DSB formation by enhancing the interaction between Rec12 and hotspots. In addition, we found that the lack of the H3K4 methyltransferase Set1 generally increased Rec12 binding to chromatin but partially reduced DSB formation at some loci, suggesting that Set1 is also involved in DSB formation. These results suggest that meiotic DSB formation is redundantly regulated by multiple chromatin-related factors including H3K9ac and Set1 in fission yeast. 相似文献
54.
Abounouh Karima Kayesh Mohammad Enamul Hoque Altawalah Haya Kitab Bouchra Murakami Shuko Ogawa Shintaro Tanaka Yasuhito Dehbi Hind Pineau Pascal Kohara Michinori Benjelloun Soumaya Tsukiyama-Kohara Kyoko Ezzikouri Sayeh 《Molecular biology reports》2022,49(1):403-412
Molecular Biology Reports - Hepatitis B Virus (HBV) is the most common cause of chronic liver disease worldwide. The mechanisms that regulate HBV viral replication remain poorly defined. Here, we... 相似文献
55.
Kazuko Wada Shintaro Nomura Eiichi Morii Yukihiko Kitamura Yasuko Nishizawa Akira Miyake Nobuyuki Terada 《The Journal of steroid biochemistry and molecular biology》1996,59(5-6):367-375
To examine the roles played by transforming growth factors (TGF)-β1, -β2, -β3, and TGF-β type II receptors in the induction of apoptosis in the mouse uterine epithelium after estrogen deprivation, we investigated the expression of their mRNAs and the mRNA of sulfated glycoprotein-2 (SGP-2). Pellets containing 100 μg estradiol-17β (E2) were implanted into ovariectomized mice and removed four days later. Apoptotic indices (percentage of apoptotic cells) of both luminal and glandular epithelia increased after E2 pellets were removed, but administration of progesterone (P), 5-dihydrotestosterone (DHT), or continued implantation of E2 pellets suppressed this increase. Levels of mRNAs of TGF-β1, -β2, and -β3, and SGP-2 did not increase after estrogen deprivation. However, estrogen deprivation caused a gradual increase in the level of TGF-β type II receptor mRNA, and its level increased about six-fold six days later. Moreover, E2, P, and DHT markedly decreased the level of TGF-β type II receptor mRNA. In situ hybridization demonstrated that mRNAs of TGF-β1, -β2, -β3 and TGF-β type II receptor were localized to the epithelium. Exogenous administration of TGF-β1 into the uterine stroma induced apoptosis in the epithelium, a finding that suggests that signals produced by TGF-βs can induce apoptosis. Therefore, the present results suggest that increased sensitivity of uterine epithelial cells to TGF-βs, as demonstrated by an increase in TGF-β type II receptor mRNA, is involved in the induction of apoptosis after estrogen deprivation, although signals produced by TGF-βs do not appear sufficient to induce apoptosis. 相似文献
56.
Hirofumi Nishida Akio Matsumoto Naohiro Tomono Takahiro Hanakai Shintaro Harada Haruaki Nakaya 《FEBS letters》2010,584(10):2161-2166
Over the past decades there has been considerable progress in understanding the multifunctional roles of mitochondrial ion channels in metabolism, energy transduction, ion transport, signaling, and cell death. Recent data have suggested that some of these channels function under physiological condition, and others may be activated in response to pathological insults and play a key role in cytoprotection. This review outlines our current understanding of the molecular identity and pathophysiological roles of the mitochondrial ion channels in the heart with particular emphasis on cardioprotection against ischemia/reperfusion injury, and future research on mitochondrial ion channels. 相似文献
57.
Kazuhiko Shimizu Shunichi Morikawa Shuji Kitahara Taichi Ezaki 《Cell and tissue research》2009,338(3):423-432
Although the immunological and hemodynamical significance of the spleen is of great importance, few reports detail the lymphatic
vessels in this organ. We have used an immunohistochemical three-dimensional imaging technique to characterize lymphatic vessels
in the normal mouse spleen and have successfully demonstrated their spatial relationship to the blood vascular system for
the first time. Lymphatic markers, such as LYVE-1, VEGFR-3, and podoplanin, show different staining patterns depending on
their location in the spleen. LYVE-1-positive lymphatic vessels run reverse to the arterial blood flow along the central arteries
in the white pulp and trabecular arteries and exit the spleen from the hilum. These lymphatic vessels are surrounded by type
IV collagen, indicating that they are collecting lymphatic vessels rather than lymphatic capillaries. Podoplanin is expressed
not only in lymphatic vessels, but also in stromal cells in the white pulp. These podoplanin-positive cells form fine meshworks
surrounding the lymphatic vessels and central arteries. Following intravenous transplantation of lymphocytes positive for
green fluorescent protein (GFP+) into normal recipient mice, donor cells appear in the meshworks within 1 h and accumulate in the lymphatic vessels within
6 h after injection. The GFP+ cells further accumulate in a draining celiac lymph node through the efferent lymphatic vessels from the hilum. These meshworks
might therefore act as an extravascular lymphatic pathway and, together with ordinary lymphatic vessels, play a primary role
in the cell traffic of the spleen, additional to the blood circulatory system. 相似文献
58.
Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes
Mycobacterium tuberculosis (M. tb) is an intracellular pathogen that can replicate within infected macrophages. The ability of M. tb to arrest phagosome maturation is believed to facilitate its intracellular multiplication. Rab GTPases regulate membrane trafficking, but details of how Rab GTPases regulate phagosome maturation and how M. tb modulates their localization during inhibiting phagolysosome biogenesis remain elusive. We compared the localization of 42 distinct Rab GTPases to phagosomes containing either Staphylococcus aureus or M. tb. The phagosomes containing S. aureus were associated with 22 Rab GTPases, but only 5 of these showed similar localization kinetics as the phagosomes containing M. tb. The Rab GTPases responsible for phagosome maturation, phagosomal acidification and recruitment of cathepsin D were examined in macrophages expressing the dominant-negative form of each Rab GTPase. LysoTracker staining and immunofluorescence microscopy revealed that Rab7, Rab20 and Rab39 regulated phagosomal acidification and Rab7, Rab20, Rab22b, Rab32, Rab34, Rab38 and Rab43 controlled the recruitment of cathepsin D to the phagosome. These results suggest that phagosome maturation is achieved by a series of interactions between Rab GTPases and phagosomes and that differential recruitment of these Rab GTPases, except for Rab22b and Rab43, to M. tb-containing phagosomes is involved in arresting phagosome maturation and inhibiting phagolysosome biogenesis. 相似文献
59.
Changes in the antibiotic production by co-culture of Rhizopus peka P8 and Bacillus subtilis IFO3335
Tsubasa Fukuda Shintaro Yamamoto Hiroshi Morita 《World journal of microbiology & biotechnology》2008,24(9):1893-1899
The co-culture of Bacillus subtilis IFO 3335 with Rhizopus peka P8 or Rhizopus oligosporus P12 in liquid medium was found to increase production of antibiotic activity and to alter the spectrum of activity relative
to the pure cultures. However, a mixed culture of Rhizopus
arrhizus P7 and Rhizopus oryzae P17 did not produce antibiotic activity. The concentration, ratio, and time of addition of B. subtilis to the R. peka culture was found to influence antibiotic yields. Solid-state fermentations using mixed cultures of R. peka and B. subtilis were investigated. The growth of Escherichia coli IFO 3792 as a target bacterium was inhibited by the mixed culture. These results suggest the possibility of biopreservation
of fermented foods by novel co-culture systems. 相似文献
60.
Hirohito Mori Hideki Kobara Takaaki Tsushimi Noriko Nishiyama Shintaro Fujihara Tsutomu Masaki 《PloS one》2015,10(4)