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131.
Kouchi Z Fujiwara Y Yamaguchi H Nakamura Y Fukami K 《Biochemical and biophysical research communications》2011,(4):384-529
Numerous epidemiological data indicate that vitamin D receptor (VDR) signaling induced by its ligand or active metabolite 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) has anti-cancer activity in several colon cancers. 1α,25(OH)2D3 induces the epithelial differentiation of SW480 colon cancer cells expressing VDR (SW480-ADH) by upregulating E-cadherin expression; however, its precise mechanism remains unknown. We found that phosphatidylinositol-5-phosphate 4-kinase type II beta (PIPKIIβ) but not PIPKIIα is required for VDR-mediated E-cadherin induction in SW480-ADH cells. The syntenin-2 postsynaptic density protein/disc large/zona occludens (PDZ) domain and pleckstrin homology domain of phospholipase C-delta1 (PLCδ1 PHD) possess high affinity for phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) mainly localized to the nucleus and plasma membrane, respectively. The expression of syntenin-2 PDZ but not PLCδ1 PHD inhibited 1α,25(OH)2D3-induced E-cadherin upregulation, suggesting that nuclear PI(4,5)P2 production mediates E-cadherin expression through PIPKIIβ in a VDR-dependent manner. PIPKIIβ is also involved in the suppression of the cell motility induced by 1α,25(OH)2D3. These results indicate that PIPKIIβ-mediated PI(4,5)P2 signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation. 相似文献
132.
M Hayakawa S Sugiyama T Takamura K Yokoo M Iwata K Suzuki F Taki S Takahashi T Ozawa 《Biochemical and biophysical research communications》1986,137(1):424-430
An epoxy derivative of linoleate, 9,10-epoxy-12-octadecenoate, was demonstrated to be biosynthesized by neutrophils from various sources such as canine and human blood, and guinea-pig peritonea. It was nominated as leukotoxin from its 'toxic' activity onto mitochondrial respiration. From the reaction mixture of leukocytes with linoleate, an isomer of leukotoxin, 12,13-epoxy-9-octadecenoate, and a 'non-toxic' hydroxy derivative of linoleate, 9-hydroxy-12-octadecenoate, were detected. Such a cascade reaction of linoleate by leukocytes was discussed. Biosynthesis of leukotoxin by neutrophils was substantially enhanced by the presence of calcium ion and calcium-ionophore, A23187. Neutrophils contained leukotoxin, ca. 7 f moles/cell, which was extractable by 60% ethanol, but little of the isomer. 相似文献
133.
Kiyotaka Akiyama Hiroyuki Morita Shiro Suetsugu Seiko Kuraba Yasuharu Numata Yoshihisa Yamamoto Kiyoko Inui Terukuni Ideura Noriko Wakisaka Kiyoko Nakano Hiroaki Oniki Tadaomi Takenawa Mutsushi Matsuyama Ashio Yoshimura 《Mammalian genome》2008,19(1):41-50
The BUF/Mna strain of rat is a model of focal and segmental glomerulosclerosis (FSGS) in which a quantitative trait locus
(QTL) for proteinuria, Pur1, has been identified. The aim of the present study was to identify candidates for the Pur1 gene. To narrow the Pur1 QTL, we performed fine QTL mapping and single nucleotide polymorphism (SNP) genotyping. To identify candidate genes, sequencing
and gene-expression analyses of all genes contained in the narrowed locus were conducted. The narrowed Pur1 region contained 25 genes. Among these genes, only the Arp3 gene was mutated in the BUF/Mna strain; it contained a missense mutation that caused an L111F substitution. This leucine is conserved across species. Gene-expression analysis failed to identify any other candidate genes
for Pur1. Arp3-mediated actin assembly abnormalities were visible in immunohistochemical and electron microscopic examinations of
podocytes in old BUF/Mna rats. Taken together, these data suggest that Arp3 is a candidate for the Pur1 gene. This observation is consistent with our growing recognition that abnormal signaling-induced assembly of actin in podocytes
leads to the development of FSGS.
Nucleotide sequence data reported in this article are available in the DDBJ/EMBL/GenBank database under accession numbers
AB292042-292043 and AB294577-294580. 相似文献
134.
135.
Ichinohe M Nakamura Y Sai K Nakahara M Yamaguchi H Fukami K 《Biochemical and biophysical research communications》2007,356(4):912-918
Phospholipase C (PLC) is a key enzyme in phosphoinositide signaling. We previously generated PLC-delta1 knockout (KO) mice and found that these mice showed remarkable hair loss caused by abnormalities in hair follicle structures. Here we show that the skin of PLC-delta1 KO mice displays typical inflammatory phenotypes, including increased dermal cellularity, leukocyte infiltration, and expression of pro-inflammatory cytokines. In addition, exogenously expressed PLC-delta1 attenuates lipopolysaccharide-induced expression of IL-1beta, a pro-inflammatory cytokine, in an enzymatic activity-dependent manner. Furthermore, suppression of skin inflammation by anti-inflammatory reagents cured the epidermal hyperplasia in PLC-delta1 KO mice. Taken together, these results indicate that lack of PLC-delta1 induces skin inflammation and that the epidermal hyperplasia in PLC-delta1 KO mice is caused by skin inflammation. Our results also suggest that PLC-delta1 regulates homeostasis of the immune system in skin. 相似文献
136.
Okajima M Takamura M Véquaud P Parent R Lavallée M 《American journal of physiology. Heart and circulatory physiology》2003,284(2):H501-H510
Shear stress-dependent nitric oxide (NO) formation prevents immoderate vascular constriction. We examined whether shear stress-dependent NO formation limits exercise-induced coronary artery constriction after beta-adrenergic receptor blockade in dogs. Control exercise led to increases (P < 0.01) in coronary blood flow (CBF) by 38 +/- 5 ml/min from 41 +/- 5 ml/min and in the external diameter of epicardial coronary arteries (CD) by 0.24 +/- 0.03 mm from 3.33 +/- 0.20 mm. CD and shear stress were linearly related. After propranolol, CD fell (P < 0.01) during exercise (0.08 +/- 0.03 from 3.23 +/- 0.19 mm), and the slope of the relationship between CD and shear stress was reduced (P < 0.01). This slope was not further altered by the additional blockade of NO formation. In propranolol-treated resting dogs, flow-dependent effects of intracoronary adenosine to mimic exercise-induced increases in shear stress (after propranolol) led to increases (P < 0.01) in CD (0.09 +/- 0.02 from 3.68 +/- 0.27 mm). Thus both shear stress-dependent NO formation and beta-adrenergic receptor activation are required to cause CD dilation during exercise. Suppression of beta-adrenergic receptor activation leads to impaired shear stress-dependent NO formation and allows alpha-adrenergic constriction to become dominant. 相似文献
137.
Yuki Taga Masashi Kusubata Kiyoko Ogawa-Goto Shunji Hattori 《The Journal of biological chemistry》2016,291(2):837-847
3-Hydroxyproline (3-Hyp), which is unique to collagen, is a fairly rare post-translational modification. Recent studies have suggested a function of prolyl 3-hydroxylation in fibril assembly and its relationships with certain disorders, including recessive osteogenesis imperfecta and high myopia. However, no direct evidence for the physiological and pathological roles of 3-Hyp has been presented. In this study, we first estimated the overall alterations in prolyl hydroxylation in collagens purified from skin, bone, and tail tendon of 0.5–18-month-old rats by LC-MS analysis with stable isotope-labeled collagen, which was recently developed as an internal standard for highly accurate collagen analyses. 3-Hyp was found to significantly increase in tendon collagen until 3 months after birth and then remain constant, whereas increased prolyl 3-hydroxylation was not observed in skin and bone collagen. Site-specific analysis further revealed that 3-Hyp was increased in tendon type I collagen in a specific sequence region, including a previously known modification site at Pro707 and newly identified sites at Pro716 and Pro719, at the early ages. The site-specific alterations in prolyl 3-hydroxylation with aging were also observed in bovine Achilles tendon. We postulate that significant increases in 3-Hyp at the consecutive modification sites are correlated with tissue development in tendon. The present findings suggest that prolyl 3-hydroxylation incrementally regulates collagen fibril diameter in tendon. 相似文献
138.
T Moriyama H Takamura H Narita K Tanaka T Matsuura M Kito 《Journal of biochemistry》1988,103(6):901-902
The thromboxane A2 antagonist, ONO-3708, completely inhibited the increase in cytosolic free Ca2+ in human platelets during activation with collagen. Half-maximal Ca2+ release and influx required about 3 and 4 nM STA2, a stable thromboxane A2 mimetic, respectively. However, half maximal activation of phospholipase C required about 18 nM STA2. This suggests that thromboxane A2 directly causes Ca2+ mobilization without further activation of phospholipase C during activation of human platelets with collagen. 相似文献
139.
Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein: implications for the mechanism of tau aggregation 总被引:1,自引:0,他引:1
Golam Sadik Toshihisa Tanaka Kiyoko Kato Hidenaga Yamamori Begum Nurun Nessa Takashi Morihara Masatoshi Takeda 《Journal of neurochemistry》2009,108(1):33-43
The microtubule associated protein tau is a major component of neurofibrillary tangles in Alzheimer disease brain, however the neuropathological processes behind the formation of neurofibrillary tangles are still unclear. Previously, 14-3-3 proteins were reported to bind with tau. 14-3-3 Proteins usually bind their targets through specific serine/threonine –phosphorylated motifs. Therefore, the interaction of tau with 14-3-3 mediated by phosphorylation was investigated. In this study, we show that the phosphorylation of tau by either protein kinase A (PKA) or protein kinase B (PKB) enhances the binding of tau with 14-3-3 in vitro . The affinity between tau and 14-3-3 is increased 12- to 14-fold by phosphorylation as determined by real time surface plasmon resonance studies. Mutational analyses revealed that Ser214 is critical for the phosphorylation-mediated interaction of tau with 14-3-3. Finally, in vitro aggregation assays demonstrated that phosphorylation by PKA/PKB inhibits the formation of aggregates/filaments of tau induced by 14-3-3. As the phosphorylation at Ser214 is up-regulated in fetal brain, tau's interaction with 14-3-3 may have a significant role in the organization of the microtubule cytoskeleton in development. Also as the phosphorylation at Ser214 is up-regulated in Alzheimer's disease brain, tau's interaction with 14-3-3 might be involved in the pathology of this disease. 相似文献
140.
Hirotaka Imai Kyoko Shinya Ryo Takano Maki Kiso Yukiko Muramoto Saori Sakabe Shin Murakami Mutsumi Ito Shinya Yamada Mai thi Quynh Le Chairul A. Nidom Yuko Sakai-Tagawa Kei Takahashi Yasuyuki Omori Takeshi Noda Masayuki Shimojima Satoshi Kakugawa Hideo Goto Kiyoko Iwatsuki-Horimoto Taisuke Horimoto Yoshihiro Kawaoka 《PLoS pathogens》2010,6(9)
Highly pathogenic H5N1 influenza A viruses have spread across Asia, Europe, and Africa. More than 500 cases of H5N1 virus infection in humans, with a high lethality rate, have been reported. To understand the molecular basis for the high virulence of H5N1 viruses in mammals, we tested the virulence in ferrets of several H5N1 viruses isolated from humans and found A/Vietnam/UT3062/04 (UT3062) to be the most virulent and A/Vietnam/UT3028/03 (UT3028) to be avirulent in this animal model. We then generated a series of reassortant viruses between the two viruses and assessed their virulence in ferrets. All of the viruses that possessed both the UT3062 hemagglutinin (HA) and nonstructural protein (NS) genes were highly virulent. By contrast, all those possessing the UT3028 HA or NS genes were attenuated in ferrets. These results demonstrate that the HA and NS genes are responsible for the difference in virulence in ferrets between the two viruses. Amino acid differences were identified at position 134 of HA, at positions 200 and 205 of NS1, and at positions 47 and 51 of NS2. We found that the residue at position 134 of HA alters the receptor-binding property of the virus, as measured by viral elution from erythrocytes. Further, both of the residues at positions 200 and 205 of NS1 contributed to enhanced type I interferon (IFN) antagonistic activity. These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals. 相似文献