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971.
Takashi Osanai Keiji Numata Akira Oikawa Ayuko Kuwahara Hiroko Iijima Yoshiharu Doi Kan Tanaka Kazuki Saito Masami Yokota Hirai 《DNA research》2013,20(6):525-535
Because cyanobacteria directly harvest CO2 and light energy, their carbon metabolism is important for both basic and applied sciences. Here, we show that overexpression of the sigma factor sigE in Synechocystis sp. PCC 6803 widely changes sugar catabolism and increases production of the biodegradable polyester polyhydroxybutyrate (PHB) during nitrogen starvation. sigE overexpression elevates the levels of proteins implicated in glycogen catabolism, the oxidative pentose phosphate pathway, and polyhydroxyalkanoate biosynthesis. PHB accumulation is enhanced by sigE overexpression under nitrogen-limited conditions, yet the molecular weights of PHBs synthesized by the parental glucose-tolerant and sigE overexpression strain are similar. Although gene expression induced by nitrogen starvation is changed and other metabolites (such as GDP-mannose and citrate) accumulate under sigE overexpression, genetic engineering of this sigma factor altered the metabolic pathway from glycogen to PHB during nitrogen starvation. 相似文献
972.
Unique "delta lock" structure of telmisartan is involved in its strongest binding affinity to angiotensin II type 1 receptor 总被引:1,自引:0,他引:1
Ohno K Amano Y Kakuta H Niimi T Takakura S Orita M Miyata K Sakashita H Takeuchi M Komuro I Higaki J Horiuchi M Kim-Mitsuyama S Mori Y Morishita R Yamagishi S 《Biochemical and biophysical research communications》2011,404(1):434-437
Angiotensin II type 1 receptor (AT1 receptor) blockers (ARBs) are one of the most popular anti-hypertensive agents. Control of blood pressure (BP) by ARBs is now a therapeutic target for the organ protection in patients with hypertension. Recent meta-analysis demonstrated the possibility that telmisartan was the strongest ARB for the reduction of BP in patients with essential hypertension. However, which molecular interactions of telmisartan with the AT1 receptor could explain its strongest BP lowering activity remains unclear. To address the issue, we constructed models for the interaction between commonly used ARBs and AT1 receptor and compared the docking model of telmisartan with that of other ARBs. Telmisartan has a unique binding mode to the AT1 receptor due to its distal benzimidazole portion. This unique portion could explain the highest molecular lipophilicity, the greatest volume distribution and the strongest binding affinity of telmisartan to AT1 receptor. Furthermore, telmisartan was found to firmly bind to the AT1 receptor through the unique “delta lock” structure. Our present study suggests that due to its “delta lock” structure, telmisartan may be superior to other ARBs in halting cardiovascular disease in patients with hypertension. 相似文献
973.
Yamauchi M Suzuki K Oka Y Suzuki M Kondo H Yamashita S 《Biochemical and biophysical research communications》2011,416(1-2):111-118
It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs. 相似文献
974.
Water can pass through biological membranes via two pathways: simple diffusion through the lipid bilayer, or water-selective facilitated diffusion through aquaporins (AQPs). Although AQPs play an important role in osmotic water permeability (Pf), the role of AQPs in diffusional water permeability remains unclear because of the difficulty of measuring diffusional water permeability (Pd). Here, we report an accurate and instantaneous method for measuring the Pd of a single HeLa S3 cell using coherent anti-Stokes Raman scattering (CARS) microscopy with a quick perfusion device for H2O/D2O exchange. Ultra-high-speed line-scan CARS images were obtained every 0.488 ms. The average decay time constant of CARS intensities (τCARS) for the external solution H2O/D2O exchange was 16.1 ms, whereas the intracellular H2O/D2O exchange was 100.7 ± 19.6 ms. To evaluate the roles of AQP in diffusional water permeability, AQP4 fused with enhanced green fluorescent protein (AQP4-EGFP) was transiently expressed in HeLa S3 cells. The average τCARS for the intracellular H2O/D2O exchange in the AQP4-EGFP-HeLa S3 cells was 43.1 ± 15.8 ms. We also assessed the cell volume and the cell surface area to calculate Pd. The average Pd values for the AQP4-EGFP-HeLa S3 cells and the control EGFP-HeLa S3 cells were 2.7 ± 1.0 × 10−3 and 8.3 ± 2.6 × 10−4 cm/s, respectively. AQP4-mediated water diffusion was independent of the temperature but was dependent on the expression level of the protein at the plasma membrane. These results suggest the possibility of using CARS imaging to investigate the hydrodynamics of single mammalian cells as well as the regulation of AQPs. 相似文献
975.
Miyazawa K 《Journal of biochemistry》2011,149(1):1-3
Arkadia, also known as ring finger 111 (Rnf111), is an E3 ubiquitin ligase that amplifies transforming growth factor (TGF)-β family signalling through degradation of negative TGF-β signal regulators, i.e. Smad7, c-Ski and SnoN. Arkadia plays critical roles in early embryonic development through modulation of nodal signalling, as well as progression of tissue fibrosis and cancer through regulation of TGF-β signalling. Recent findings suggest that, similar to other ubiquitin ligases, including Smurf1 and 2, Arkadia regulates signalling pathways other than those of the TGF-β family. Arkadia interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signalling pathways. 相似文献
976.
Tokura Y Nakayama Y Fukada S Nara N Yamamoto H Matsuda R Hara T 《Journal of biochemistry》2011,149(1):43-48
Thymosin β4 (Tβ4) is a major intracellular G-actin-sequestering peptide. There is increasing evidence to support important extracellular functions of Tβ4 related to angiogenesis, wound healing and cardiovascular regeneration. We investigated the expression of 'Tβ4' and 'thymosin β10', a closely related peptide, during skeletal muscle regeneration in mice and chemotactic responses of myoblasts to these peptides. The mRNA levels of 'Tβ4' and 'thymosin β10' were up-regulated in the early stage of regenerating muscle fibres and inflammatory haematopoietic cells in the injured skeletal muscles of mice. We found that both Tβ4 and its sulphoxized form significantly accelerated wound closure and increased the chemotaxis of C2C12 myoblastic cells. Furthermore, we showed that primary myoblasts and myocytes derived from muscle satellite cells of adult mice were chemoattracted to sulphoxized form of Tβ4. These data indicate that muscle injury enhances the local production of Tβ4, thereby promoting the migration of myoblasts to facilitate skeletal muscle regeneration. 相似文献
977.
Fujinaga R Takeshita Y Yoshioka K Nakamura H Shinoda S Islam MN Jahan MR Yanai A Kokubu K Shinoda K 《Experimental cell research》2011,(12):1689-1700
The stigmoid body (STB) is a cytoplasmic inclusion containing huntingtin-associated protein 1 (HAP1), and HAP1/STB formation is induced by transfection of the HAP1 gene into cultured cells. In the present study, we examined the intracellular colocalization of HAP1/STBs with steroid hormone receptors (SHRs), including the androgen receptor (AR), estrogen receptor, glucocorticoid receptor (GR), and mineralocorticoid receptor, in COS-7 cells cotransfected with HAP1 and each receptor. We found that C-terminal ligand-binding domains of all SHRs had potential for colocalization with HAP1/STBs, whereas only AR and GR were clearly colocalized with HAP1/STBs when each full-length SHR was coexpressed with HAP1. In addition, it appeared that HAP1/STBs did not disrupt GR and AR functions because the receptors on HAP1/STBs maintained nuclear translocation activity in response to their specific ligands. When the cells were treated with a proteasome inhibitor, GR and AR localized outside HAP1/STBs translocated into the nucleus, whereas the receptors colocalized with HAP1/STBs persisted in their colocalization even after treatment with their ligands. Therefore, HAP1/STBs may be involved in cytoplasmic modifications of the nuclear translocation of GR and AR in a ubiquitin–proteasome system. 相似文献
978.
Fukumoto T Kano A Ohtani K Yamasaki-Kokudo Y Kim BG Hosotani K Saito M Shirakawa C Tajima S Izumori K Ohara T Shigematsu Y Tanaka K Ishida Y Nishizawa Y Tada Y Ichimura K Gomi K Akimitsu K 《Planta》2011,234(6):1083-1095
One of the rare sugars, D-allose, which is the epimer of D-glucose at C3, has an inhibitory effect on rice growth, but the molecular mechanisms of the growth inhibition by D-allose were unknown. The growth inhibition caused by D-allose was prevented by treatment with hexokinase inhibitors, D-mannoheptulose and N-acetyl-D-glucosamine. Furthermore, the Arabidopsis glucose-insensitive2 (gin2) mutant, which is a loss-of-function mutant of the glucose sensor AtHXK1, showed a D-allose-insensitive phenotype. D-Allose strongly inhibited the gibberellin-dependent responses such as elongation of the second leaf sheath and induction of α-amylase in embryo-less half rice seeds. The growth of the slender rice1 (slr1) mutant, which exhibits a constitutive gibberellin-responsive phenotype, was also inhibited by D-allose, and the growth inhibition of the slr1 mutant by D-allose was also prevented by D-mannoheptulose treatment. The expressions of gibberellin-responsive genes were down-regulated by D-allose treatment, and the down-regulations of gibberellin-responsive genes were also prevented by D-mannoheptulose treatment. These findings reveal that D-allose inhibits the gibberellin-signaling through a hexokinase-dependent pathway. 相似文献
979.
As neuroactive steroids, sex steroid hormones have non-reproductive effects. We previously reported that 17β-estradiol (βE2) had protective effects against gentamicin (GM) ototoxicity in the cochlea. In the present study, we examined whether the protective action of βE2 on GM ototoxicity is mediated by the estrogen receptor (ER) and whether other estrogens (17α-estradiol (αE2), estrone (E1), and estriol (E3)) and other neuroactive steroids, dehydroepiandrosterone (DHEA) and progesterone (P), have similar protective effects. The basal turn of the organ of Corti was dissected from Sprague-Dawley rats and cultured in a medium containing 100 μM GM for 48 h. The effects of βE2 and ICI 182,780, a selective ER antagonist, were examined. In addition, the effects of other estrogens, DHEA and P were tested using this culture system. Loss of outer hair cells induced by GM exposure was compared among groups. βE2 exhibited a protective effect against GM ototoxicity, but its protective effect was antagonized by ICI 182,780. αE2, E1, and E3 also protected hair cells against gentamicin ototoxicity. DHEA showed a protective effect; however, the addition of ICI 182,780 did not affect hair cell loss. P did not have any effect on GM-induced outer hair cell death. The present findings suggest that estrogens and DHEA are protective agents against GM ototoxicity. The results of the ER antagonist study also suggest that the protective action of βE2 is mediated via ER but that of DHEA is not related to its conversion to estrogen and binding to ER. Further studies on neuroactive steroids may lead to new insights regarding cochlear protection. 相似文献
980.
Hou IC Suzuki C Kanegawa N Oda A Yamada A Yoshikawa M Yamada D Sekiguchi M Wada E Wada K Ohinata K 《Journal of neurochemistry》2011,119(4):785-790
β-Lactotensin (His-Ile-Arg-Leu) is a bioactive peptide derived from bovine milk β-lactoglobulin, acting as a natural agonist for neurotensin receptors. We found that β-lactotensin exhibited anxiolytic-like activity in an elevated plus-maze test after its intraperitoneal (i.p.) administration in mice. β-Lactotensin was also orally active. The anxiolytic-like activity of β-lactotensin after i.p. administration was blocked by levocabastine, an antagonist for the neurotensin NTS(2) receptor. β-Lactotensin had anxiolytic-like activity in wild-type but not Ntsr2-knockout mice. β-Lactotensin increased intracellular Ca(2+) flux in glial cells derived from wild-type mice but not Ntsr2 knockout mice. These results suggest that β-lactotensin acts as an NTS(2) receptor agonist having anxiolytic-like activity. The anxiolytic-like activity of β-lactotensin was also blocked by SCH23390 and SKF83566, antagonists for dopamine D(1) receptor, but not by raclopride, an antagonist for D(2) receptor. Taken together, β-lactotensin may exhibit anxiolytic-like activity via NTS(2) receptor followed by D(1) receptor. 相似文献