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961.
Muthangi Subramanyam Nobuyuki Takahashi Yuichi Hasegawa Tatsuma Mohri Yasunobu Okada 《The Journal of biological chemistry》2010,285(9):6109-6117
Most animal cell types regulate their cell volume after an osmotic volume change. The regulatory volume increase (RVI) occurs through uptake of NaCl and osmotically obliged water after osmotic shrinkage. However, apoptotic cells undergo persistent cell shrinkage without showing signs of RVI. Persistence of the apoptotic volume decrease is a prerequisite to apoptosis induction. We previously demonstrated that volume regulation is inhibited in human epithelial HeLa cells stimulated with the apoptosis inducer. Here, we studied signaling mechanisms underlying the apoptotic inhibition of RVI in HeLa cells. Hypertonic stimulation was found to induce phosphorylation of a Ser/Thr protein kinase Akt (protein kinase B). Shrinkage-induced Akt activation was essential for RVI induction because RVI was suppressed by an Akt inhibitor, expression of a dominant negative form of Akt, or small interfering RNA-mediated knockdown of Akt1 (but not Akt2). Staurosporine, tumor necrosis factor-α, or a Fas ligand inhibited both RVI and hypertonicity-induced Akt activation in a manner sensitive to a scavenger for reactive oxygen species (ROS). Any of apoptosis inducers also induced phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) in a ROS-dependent manner. Suppression of (ASK1) expression blocked the effects of apoptosis, in hypertonic conditions, on both RVI induction and Akt activation. Thus, it is concluded that in human epithelial cells, shrinkage-induced activation of Akt1 is involved in the RVI process and that apoptotic inhibition of RVI is caused by inhibition of Akt activation, which results from ROS-mediated activation of ASK1. 相似文献
962.
Nobuyuki Itoh 《Cell and tissue research》2010,342(1):1-11
Adrenomedullin (AM) is a peptide hormone involved in the modulation of cellular growth, migration, apoptosis, and angiogenesis.
These characteristics suggest that AM is involved in the control of neural stem/progenitor cell (NSPC) biology. To explore
this hypothesis, we have obtained NSPC from the olfactory bulb of adult wild-type animals and brain conditional knockouts
for adm, the gene that produces AM. Knockout NSPC contain higher levels of hyperpolymerized tubulin and more abundant filopodia than
adm-containing cells, resulting in a different morphology in culture, whereas the size of the knockout neurospheres is smaller
than that of the wild-types. Proliferation studies have demonstrated that adm-null NSPC incorporate less 5′-bromodeoxyuridine (BrdU) than their wild-type counterparts. In contrast, BrdU studies in the
olfactory bulb of adult animals show more labeled cells in adm-null mice that in wild-types, suggesting that a compensatory mechanism exists that guarantees the sufficient production of
neural cells in this organ. In NSPC differentiation tests, lack of adm results in significantly lower proportions of neurons and astrocytes and higher proportions of oligodendrocytes. The oligodendrocytes
produced from adm-null neurospheres present an immature phenotype with fewer and shorter processes than adm-containing oligodendrocytes. Thus, AM is an important factor in regulating the proliferation and differentiation of adult
NSPC and might be used to modulate stem cell renewal and fate in protocols destined to produce neural cells for regenerative
therapies. 相似文献
963.
Endo Satoru Takada Masashi Tanaka Hiroki Onizuka Yoshihiko Tanaka Kenichi Miyahara Nobuyuki Baba Hiromi Oishi Ayumu Ishikawa Masayori Hoshi Masaharu Kimura Shinzo Minematsu Masakazu Morimune Yuki Kojima Yasuaki Shizuma Kiyoshi 《Radiation and environmental biophysics》2010,49(3):469-475
Radiation and Environmental Biophysics - This study describes measurements on secondary particles produced by a 290 MeV/n Spread Out Bragg Peak (SOBP) carbon beam. Microdosimetric... 相似文献
964.
Toshikazu Shinba Nobuyuki Ozawa Mitsunobu Yoshii Ken-ichi Yamamoto 《Neurochemical research》2010,35(3):412-417
Several lines of evidence strongly suggest that accumulation of noradrenaline (NA) in the brain may underlie the hyperarousal
symptoms experienced in post-traumatic stress disorder. In animal experiments, however, the effect of stress on NA content
appears complex; acute stress reduces the level, while chronic stress tends to increase it. To explain this discrepancy, it
is necessary to observe the long-term effects of acute stress on NA metabolism in the brain. In this study, rats were exposed
to intermittent intense footshock stress for 1 h, and the brain NA content was measured for 7 days after the stress stimulus.
Hypothalamic NA content was immediately reduced and recovered within 24 h. However, a significant NA increase was observed
7 days after the footshock. In the cerebral cortex and hippocampus, an increase in NA content was observed 1 day after the
stress and lasted for at least 7 days. The fact that the content of 3-methoxy-4-hydroxyphenylglycol, a major NA metabolite,
only transiently increased in all these regions possibly reflects NA release. These results indicate that increase in the
brain NA content can be induced by acute stress, though its emergence is delayed. Importantly, this suggests that both acute
and chronic stress may lead to NA accumulation under the same mechanism. 相似文献
965.
Toshihiro Nanki Kazuki Takada Yukiko Komano Tomohiro Morio Hirokazu Kanegane Atsuo Nakajima Peter E Lipsky Nobuyuki Miyasaka 《Arthritis research & therapy》2009,11(5):R149-11
Introduction
Accumulation of B cells in the rheumatoid arthritis (RA) synovium has been reported, and it has been thought that these cells might contribute to the pathogenesis of RA by antigen presentation, autoantibody production, and/or inflammatory cytokine production. Chemokines could enhance the accumulation of B cells in the synovium. The aims of this study were to determine chemokine receptor expression by B cells both in the peripheral blood of normal donors and subjects with RA, and at the inflammatory site in RA, and the effects of chemokines on B cell activation. 相似文献966.
Staurosporine: An Effective Inhibitor for Ca2+ /Calmodulin-Dependent Protein Kinase II 总被引:1,自引:0,他引:1
Nobuyuki Yanagihara Eiichi Tachikawa Futoshi Izumi Setsuko Yasugawa† Hideyuki Yamamoto† Eishichi Miyamoto† 《Journal of neurochemistry》1991,56(1):294-298
We investigated the effect of staurosporine on Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) purified from rat brain. (a) Staurosporine (10-100 nM) inhibited the activity of CaM kinase II. The half-maximal and maximal inhibitory concentrations were 20 and 100 nM, respectively. (b) The inhibition with staurosporine was of the noncompetitive type with respect to ATP, calmodulin, and phosphate acceptor (beta-casein). (c) Staurosporine suppressed the auto-phosphorylation of alpha- and beta-subunits of CaM kinase II at concentrations similar to those at which the enzyme activity was inhibited. (d) Staurosporine also attenuated the Ca2+/calmodulin-independent activity of the autophosphorylated CaM kinase II. These results suggest that staurosporine inhibits CaM kinase II by interacting with the catalytic domain, distinct from the ATP-binding site or substrate-binding site, of the enzyme and that staurosporine is an effective inhibitor for CaM kinase II in the cell system. 相似文献
967.
Akatsuki Kokaze Mamoru Ishikawa Naomi Matsunaga Kanae Karita Masao Yoshida Tadahiro Ohtsu Hirotaka Ochiai Takako Shirasawa Hinako Nanri Nobuyuki Saga Iichiro Ohtsu Hiromi Hoshino Yutaka Takashima 《Journal of physiological anthropology》2014,33(1)
Background
Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism reportedly modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia and abnormal glucose tolerance. The objective of this analysis was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on erythrocytic parameters in male Japanese health check-up examinees.Methods
A total of 436 men (mean age ± standard deviation, 54.1 ± 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, an exploratory cross-sectional analysis assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on red blood cell counts, hematocrit and hemoglobin was conducted.Results
For Mt5178C genotypic men, after adjustment for age, body mass index, alcohol consumption, habitual smoking and green tea consumption, coffee consumption significantly decreased red blood cell counts (P for trend = 0.022) and hemoglobin (P for trend = 0.035). The risk of anemia, defined as hemoglobin of <14 g/dL, after the aforementioned adjustment, appeared to depend on coffee consumption (P for trend = 0.078), and the adjusted odds ratio for anemia was significantly higher in men who consumed ≥4 cups of coffee per day than in those who consumed <1 cup per day (odds ratio = 3.771, 95% confidence interval: 1.088 to 13.06, P = 0.036). For Mt5178A genotypic men, coffee consumption possibly reduced the risk of anemia (P for trend = 0.049). However, after the aforementioned adjustment, the statistical significance disappeared (P for trend = 0.137).Conclusions
This exploratory cross-sectional analysis suggests that Mt5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters and the risk of anemia in male Japanese health check-up examinees. 相似文献968.
Friedrichs Steffi Takasu Yoko Kearns Peter Dagallier Bertrand Oshima Ryudai Schofield Janet Moreddu Catherine 《Transgenic research》2019,28(3-4):419-463
Transgenic Research - The “OECD Conference on Genome Editing: Applications in Agriculture—Implications for Health, Environment and Regulation” was held on the 28–29 June... 相似文献
969.
Takayasu Motoyama Yutaka Okumoto Takatoshi Tanisaka Shigeru Utsumi Nobuyuki Maruyama 《Transgenic research》2010,19(5):819-827
A transgenic rice that produces both the α′ and β subunits of β-conglycinin has been developed through the crossing of two
types of transgenic rice. Although the accumulation level of the α′ subunit in the α′β-transgenic rice was slightly lower
than that in the transgenic rice producing only the α′ subunit, the accumulation level of the β subunit in the α′β-transgenic
rice was about 60% higher than that in the transgenic rice producing only the β subunit. Results from sequential extraction
and gel-filtration experiments indicated that part of the β subunit formed heterotrimers with the α′ subunit in a similar
manner as in soybean seeds and that the heterotrimers interacted with glutelin via cysteine residues. These results imply
that the accumulation level of the β subunit in the α′β-transgenic rice increases by an indirect interaction with glutelin.
Immunoelectron microscopy revealed that the α′ and β subunits are localized in a low electron-dense region of protein body-II
(PB-II) and that α′ homotrimers in the α′β-transgenic rice seeds seem to accumulate outside of this low electron-dense region. 相似文献
970.
Long glutamine sequences (polyQ) occur in many cell proteins, and several neurodegenerative diseases result from expansion of these sequences. PolyQ-containing proteins are degraded by proteasomes, whose three active sites prefer to cleave after hydrophobic, basic, or acidic residues. We tested whether these particles can digest a polyQ chain. Eukaryotic 26S and 20S proteasomes failed to cut within stretches of 9-29Q residues in peptides. While digesting a myoglobin Q(35) fusion protein, the proteasomes spared the polyQ sequence. In contrast, archaeal proteasomes, whose 14 active sites are less specific, rapidly digested such polyQ repeats. Therefore, when degrading polyQ proteins, eukaryotic proteasomes must release aggregation-prone polyQ-containing fragments for further hydrolysis by unidentified peptidases. In polyQ diseases, such polyQ sequences (38-300Qs) exceed the lengths of normal proteasome products (2-25 residues). Occasional failure of these long undegradable sequences to exit may interfere with proteasome function and help explain why longer polyQ expansions promote early disease onset. 相似文献