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171.
Summary Using Ca2+- and K+-selective microelectrodes, the cytosolic free Ca2+ and K+ concentrations were measured in mouse fibroblastic L cells. When the extracellular Ca2+ concentration exceeded several micromoles, spontaneous oscillations of the intracellular free Ca2+ concentration were observed in the submicromolar ranges. During the Ca2+ oscillations, the membrane potential was found to oscillate concomitantly. The peak of cyclic increases in the free Ca2+ level coincided in time with the peak of periodic hyperpolarizations. Both oscillations were abolished by reducing the extracellular Ca2+ concentration down to 10–7
m or by applying a Ca2+ channel blocker, nifedipine (50 m). In the presence of 0.5mm quinine, an inhibitor of Ca2+-activated K+ channel, sizable Ca2+ oscillations still persisted, while the potential oscillations were markedly suppressed. Oscillations of the intracellular K+ concentration between about 145 and 140mm were often associated with the potential oscillations. The minimum phase of the K+ concentration was always 5 to 6 sec behind the peak hyperpolarization. Thus, it is concluded that the oscillation of membrane potential results from oscillatory increases in the intracellular Ca2+ level, which, in turn, periodically stimulate Ca2+-activated K+ channels. 相似文献
172.
Kakeya H Miyake Y Shoji M Kishida S Hayashi Y Kataoka T Osada H 《Bioorganic & medicinal chemistry letters》2003,13(21):3743-3746
We have previously reported that ECH, (2R, 3R, 4S)-2,3-epoxy-4-hydroxy-5-hydroxymethyl-6-(1E)-propenyl-cyclohex-5-en-1-one inhibits Fas-mediated apoptosis by blocking self-activation of pro-caspase-8 in the death-inducing signaling complex (DISC). A series of ECH derivatives were asymmetrically synthesized via key synthetic intermediates obtained from lipase-catalyzed kinetic resolution. Inhibitory activities of the derivatives towards death receptor-mediated apoptosis both in type I and type II cells were investigated, revealing that novel non-peptide inhibitors, RKTS-33 and RKTS-34, are effective as ECH. 相似文献
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174.
An intracellular domain with a novel sequence regulates cell surface expression and synaptic clustering of leucine‐rich repeat transmembrane proteins in hippocampal neurons 下载免费PDF全文
Keiichiro Minatohara Yasunobu Murata Yoshinori Fujiyoshi Tomoko Doi 《Journal of neurochemistry》2015,134(4):618-628
Leucine‐rich repeat transmembrane proteins (LRRTMs) are single‐spanning transmembrane proteins that belong to the family of synaptically localized adhesion molecules that play various roles in the formation, maturation, and function of synapses. LRRTMs are highly localized in the post‐synaptic density; however, the mechanisms and significance of LRRTM synaptic clustering remain unclear. Here, we focus on the intracellular domain of LRRTMs and investigate its role in cell surface expression and synaptic clustering. The deletion of 55–56 residues in the cytoplasmic tail caused significantly reduced synaptic clustering of LRRTM1–4 in rat hippocampal neurons, whereas it simultaneously resulted in augmented LRRTM1–2 cell surface expression. A series of deletions and further single amino acid substitutions in the intracellular domain of LRRTM2 demonstrated that a previously uncharacterized sequence at the region of ‐16 to ‐13 from the C‐terminus was responsible for efficient synaptic clustering and proper cell surface trafficking of LRRTMs. Furthermore, the clustering‐deficient LRRTM2 mutant lost the ability to promote the accumulation of post‐synaptic density protein‐95 (PSD‐95). These results suggest that trafficking to the cell surface and synaptic clustering of LRRTMs are regulated by a specific mechanism through this novel sequence in the intracellular domain that underlies post‐synaptic molecular assembly and maturation.
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176.
Kamijo A Sugaya T Hikawa A Yamanouchi M Hirata Y Ishimitsu T Numabe A Takagi M Hayakawa H Tabei F Sugimoto T Mise N Omata M Kimura K 《Molecular and cellular biochemistry》2006,284(1-2):175-182
Background: We reported that urinary L-FABP reflected the progression of chronic kidney disease (CKD). This study is aimed to evaluate the clinical significance
of urinary liver type fatty acid binding protein (L-FABP) as a biomarker for monitoring CKD. Methods: Urinary L-FABP was measured using human L-FABP ELISA kit (CMIC.Co., Ltd., Tokyo, Japan). The relations between urinary L-FABP and clinical parameters were evaluated in non-diabetic CKD (n = 48) for a year. In order to evaluate the influence of serum L-FABP derived from liver upon urinary L-FABP, both serum and urinary L-FABP were simultaneously measured in patients with CKD (n = 73). Results: For monitoring CKD, the cut-off value in urinary L-FABP was determined as 17.4 μg/g.cr. by using a receiver operating characteristics (ROC) curve. Renal function deteriorated
significantly more in patients with ‘high’ urinary L-FABP (n = 36) than in those with ‘low’ L-FABP (n = 12). The decrease in creatinine clearance was accompanied by an increase in urinary L-FABP, but not in urinary protein. Serum L-FABP in patients with CKD was not correlated with urinary L-FABP. Conclusion: Urinary excretion of L-FABP increases with the deterioration of renal function. Serum L-FABP did not influence on urinary L-FABP. Urinary L-FABP may be a useful clinical biomarker for monitoring CKD. 相似文献
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178.
Saito K Yajima T Kumabe S Doi T Yamada H Sad S Shen H Yoshikai Y 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(4):2496-2504
To investigate the potential role of endogenous IL-15 in mycobacterial infection, we examined protective immunity in IL-15-deficient (IL-15(-/-)) mice after infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG) or recombinant OVA-expressing BCG (rBCG-OVA). IL-15(-/-) mice exhibited an impaired protection in the lung on day 120 after BCG infection as assessed by bacterial growth. CD4(+) Th1 response capable of producing IFN-gamma was normally detected in spleen and lung of IL-15(-/-) mice on day 120 after infection. Although Ag-specific CD8 responses capable of producing IFN-gamma and exhibiting cytotoxic activity were detected in the lung on day 21 after infection with rBCG-OVA, the responses were severely impaired on days 70 and 120 in IL-15(-/-) mice. The degree of proliferation of Ag-specific CD8(+) T cells in IL-15(-/-) mice was similar to that in wild-type mice during the course of infection with rBCG-OVA, whereas sensitivity to apoptosis of Ag-specific CD8(+) T cells significantly increased in IL-15(-/-) mice. These results suggest that IL-15 plays an important role in the development of long-lasting protective immunity to BCG infection via sustaining CD8 responses in the lung. 相似文献
179.
A sustained increase of cytosolic Ca in γδ T cells triggered by co-stimulation via TCR/CD3 and LFA-1
N. Kobayashi K. Hiromatsu G. Matsuzaki M. Harada Y. Matsumoto K. Nomoto Y. Yoshikai 《Cell calcium》1997,22(6)
We previously reported that co-stimulation with LFA-1 triggered apoptosis in γδ T cells but not in αβ T cells after TCR engagement. We extended our earlier study on TCR/LFA-1 triggered apoptosis to two autoreactive TCR γδ and TCR αβ T cell clones, which were derived from syngeneic mixed lymphocyte culture of BALB/c mice. A γδ T cell clone, KM1, expressed the Vγ4 and Vδ5 genes and CD4-CD8-CD45RB+ phenotype; and an αβ T cell clone, BASL1.1, expressed Vβ6 and CD4+CD8-CD45RB+. Both clones produced Th-1-type cytokines in response to syngeneic BALB/c stimulator cells. KM1 underwent apoptosis upon stimulation with immobilized anti-CD3/LFA-1 mAbs, whereas BASL1.1 could proliferate successfully in response to stimulation with the immobilized mAbs. BASL1.1 was able to down-regulate the increased cytosolic Ca2+ after the simultaneous stimulation, but KM1 exhibited a sustained increase of cytosolic Ca2+ after stimulation via CD3 and LFA-1. Similar results with respect to the kinetics of cytosolic Ca2+ were obtained with normal heterogeneous γδ and αβ T cell populations after co-stimulation via CD3 and LFA-1. Our results suggested that persistently high levels of cytosolic Ca2+ might be related to apoptosis in γδ T cell clone triggered by costimulation via CD3 and LFA-1. 相似文献
180.
Terabayashi Y Shimizu M Kitazume T Masuo S Fujii T Takaya N 《Applied microbiology and biotechnology》2012,93(1):305-317