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961.
Yuuki Fujiwara Akiko Furuta Hisae Kikuchi Shu Aizawa Yusuke Hatanaka Chiho Konya Kenko Uchida Aya Yoshimura Yoshitaka Tamai Keiji Wada Tomohiro Kabuta 《Autophagy》2013,9(3):403-409
Regulated degradation of cellular components by lysosomes is essential to maintain biological homeostasis. In mammals, three forms of autophagy, macroautophagy, microautophagy and chaperone-mediated autophagy (CMA), have been identified. Here, we showed a novel type of autophagy, in which RNA is taken up directly into lysosomes for degradation. This pathway, which we term “RNautophagy,” is ATP-dependent, and unlike CMA, is independent of HSPA8/Hsc70. LAMP2C, a lysosomal membrane protein, serves as a receptor for this pathway. The cytosolic tail of LAMP2C specifically binds to almost all total RNA derived from mouse brain. The cytosolic sequence of LAMP2C and its affinity for RNA are evolutionarily conserved from nematodes to humans. Our findings shed light on the mechanisms underlying RNA homeostasis in higher eukaryotes. 相似文献
962.
Background
There are no reported studies on the relationship between traffic crashes and brain tissue changes in healthy drivers. The relationship between traffic crashes and leukoaraiosis, a common magnetic resonance imaging finding, was investigated in this study.Methods
A total of 3,930 automobile drivers (2,037 men and 1,893 women; age, 21–87 years) who underwent brain magnetic resonance imaging as part of total health check-ups and answered a road traffic questionnaire were examined to determine whether asymptomatic leukoaraiosis was associated with various types of traffic crashes. Multiple logistic regression analysis was performed to elucidate the relationship between leukoaraiosis and various types of traffic crashes.Results
Subcortical leukoaraiosis was diagnosed in 28.52% of all subjects, whereas periventricular leukoaraiosis was diagnosed in 9.57% of all subjects. Adjusted odds ratios for involvement in all types of traffic crashes were not significant for subjects with periventricular leukoaraiosis; however, they were significant for subjects with multiple and large multiple subcortical leukoaraiosis. Adjusted odds ratios for involvement in crashes at crossroads were 1.09 (95% confidence interval [CI], 0.60–2.00) for subjects with single subcortical leukoaraiosis, 3.35 (95% CI, 2.36–4.77) for subjects with multiple subcortical leukoaraiosis, and 2.45 (95% CI, 2.36–4.98) for subjects with large multiple subcortical leukoaraiosis. Periventricular leukoaraiosis was not significantly associated with crossroad crashes. Involvement in crashes of any type, parking lot crashes, and rear-end collisions showed no significant association with either subcortical or periventricular leukoaraiosis.Conclusions
Multiple subcortical leukoaraiosis, but not periventricular leukoaraiosis, is significantly associated with traffic crashes, in particular, crossroad crashes. This association is independent of sex, age, and driving exposure. To our knowledge, this is the first evidence describing the relationship between brain tissue changes and traffic crashes. 相似文献963.
Matsuzaki S Ishizuka T Yamada H Kamide Y Hisada T Ichimonji I Aoki H Yatomi M Komachi M Tsurumaki H Ono A Koga Y Dobashi K Mogi C Sato K Tomura H Mori M Okajima F 《Biochemical and biophysical research communications》2011,413(4):499-503
Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-β-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the Gq/11 protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP3) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/Gq/11 protein and inositol-1,4,5-trisphosphate-induced Ca2+ mobilization in human ASMCs. 相似文献
964.
Murata Y Furuyama I Oda S Mitani H 《Biochemical and biophysical research communications》2011,(1):92-97
Upon spinal cord injury, the myelin inhibitors, including the myelin-associated glycoprotein (MAG), Nogo-A and the oligodendrocyte myelin glycoprotein (OMgp), bind to and signal via a single neuronal receptor/co-receptor complex comprising of Nogo receptor 1(NgR1)/LINGO-1 and p75 or TROY, impeding regeneration of injured axons. We employed a cell-free system to study the binding of NgR1 to its co-receptors and the myelin inhibitor Nogo-A, and show that gangliosides mediate the interaction of NgR1 with LINGO-1. Solid phase binding assays demonstrate that the sialic acid moieties of gangliosides and the stalk of NgR1 are the principal determinants of these molecular interactions. Moreover, the tripartite complex comprising of NgR1, LINGO-1 and ganglioside exhibits stronger binding to Nogo-A (Nogo-54) in the presence of p75, suggesting the gangliosides modulate the myelin inhibitor-receptor signaling. 相似文献
965.
966.
The quantification of spontaneous calcium (Ca(2+)) oscillations (SCOs) in astrocytes presents a challenge because of the large irregularities in the amplitudes, durations, and initiation times of the underlying events. In this article, we use a stochastic context to account for such SCO variability, which is based on previous models for cellular Ca(2+) signaling. First, we found that passive Ca(2+) influx from the extracellular space determine the basal concentration of this ion in the cytosol. Second, we demonstrated the feasibility of estimating both the inositol 1,4,5-trisphosphate (IP(3)) production levels and the average number of IP(3) receptor channels in the somatic clusters from epifluorescent Ca(2+) imaging through the combination of a filtering strategy and a maximum-likelihood criterion. We estimated these two biophysical parameters using data from wild-type adult mice and age-matched transgenic mice overexpressing the 695-amino-acid isoform of human Alzheimer β-amyloid precursor protein. We found that, together with an increase in the passive Ca(2+) influx, a significant reduction in the sensitivity of G protein-coupled receptors might lie beneath the abnormalities in the astrocytic Ca(2+) signaling, as was observed in rodent models of Alzheimer's disease. This study provides new, to our knowledge, indices for a quantitative analysis of SCOs in normal and pathological astrocytes. 相似文献
967.
Two new ene-yne substituted 2,4-pentanedionatoruthenium(III) complexes formed by the Heck-like reactions in the course of the Sonogashira reactions. The two complexes are structural isomers; one is [Ru(E-1,4-mBSima)(dpm)2] and another is [Ru(E-2,4-mBSima)(dpm)2], where E-1,4-mBSima is E-3-(1,4-bis(trimethylsilyl)-1-butene-3-ynyl)-2,4-pentanedionate, E-2,4-mBSima is E-3-(2,4-bis(trimethylsilyl)-1-butene-3-ynyl)-2,4-pentanedionate, and dpm is dipivaloylmethanate (2,2,6,6-tetramethylheptan-3,5-dionate). Both of complexes have been characterized by 1H NMR and infrared spectroscopies, mass spectrometry, and electrochemistry. [Ru(E-1,4-mBSima)(dpm)2] has also been characterized by X-ray crystallography. The ruthenium(III) is coordinated in an octahedral arrangement by the oxygen atoms of three β-diketonate ligands. The dihedral angle between the 2,4-pentanedionato chelate ring and the ene-yne plane on the E-1,4-mBSima ligand is 91°. The ene-yne group in [Ru(E-1,4-mBSima)(dpm)2] is fixed either in the solution state suggested by the 1H NMR spectrum with no symmetry. 相似文献
968.
Yamamoto Y Harashima A Saito H Tsuneyama K Munesue S Motoyoshi S Han D Watanabe T Asano M Takasawa S Okamoto H Shimura S Karasawa T Yonekura H Yamamoto H 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(5):3248-3257
Septic shock is a severe systemic response to bacterial infection. Receptor for advanced glycation end products (RAGE) plays a role in immune reactions to recognize specific molecular patterns as pathogen recognition receptors. However, the interaction between LPS, the bioactive component of bacterial cell walls, and RAGE is unclear. In this study, we found direct LPS binding to RAGE by a surface plasmon resonance assay, a plate competition assay, and flow cytometry. LPS increased TNF-α secretion from peritoneal macrophages and an NF-κB promoter-driven luciferase activity through RAGE. Blood neutrophils and monocytes expressed RAGE, and TLR2 was counterregulated in RAGE(-/-) mice. After LPS injection, RAGE(+/+) mice showed a higher mortality, higher serum levels of IL-6, TNF-α, high mobility group box 1, and endothelin-1, and severe lung and liver pathologies compared with RAGE(-/-) mice without significant differences in plasma LPS level. Administration of soluble RAGE significantly reduced the LPS-induced cytokine release and tissue damage and improved the LPS-induced lethality even in RAGE(-/-) as well as RAGE(+/+) mice. The results thus suggest that RAGE can associate with LPS and that RAGE system can regulate inflammatory responses. Soluble RAGE would be a therapeutic tool for LPS-induced septic shock. 相似文献
969.
Thermoperiodic regulation of the circadian eclosion rhythm in the flesh fly, Sarcophaga crassipalpis
We recorded the eclosion time of the flesh fly, Sarcophaga crassipalpis, at different depths in the outdoor soil and under temperature cycles with various amplitudes in the laboratory, to examine the timing adjustment of eclosion in response to temperature cycles and their amplitudes in the pupal stage. In the soil, most eclosions occurred in the late morning, which was consistent with the eclosion time under pseudo-sinusoidal temperature cycles in the laboratory. The circadian clock controlling eclosion was reset by temperature cycles and free-ran with a period close to 24 h. This clock likely helps pupae eclose at an optimal time even when the soil temperature does not show clear daily fluctuations. The eclosion phase of the circadian clock progressively advanced as the amplitude of the pseudo-sinusoidal temperature cycle decreased. This response allows pupae located at any depth in the soil to eclose at the appropriate time despite the depth-dependent phase delay of the temperature change. In contrast, the abrupt temperature increase in square-wave temperature cycles reset the phase of the circadian clock to the increasing time, regardless of the temperature amplitude. The rapid temperature increase may act as the late-morning signal for the eclosion clock. 相似文献
970.
M. Sheikh Mohamed Srivani VeeranarayananAby Cheruvathoor Poulose Yutaka NagaokaHiroaki Minegishi Yasuhiko YoshidaToru Maekawa D. Sakthi Kumar 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014