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71.
Natsumi Doi Yuuki Kunimatsu Kouhei Fujiura Hiro Togari Kenji Minagi Koichi Nakaoji Kazuhiko Hamada Achim Temme Masaaki Tatsuka 《Journal of cellular physiology》2019,234(9):15134-15146
The molecular signals that regulate mitotic spindle orientation to determine the proper division axis play a critical role in the development and maintenance of tissue homeostasis. However, deregulation of signaling events can result in spindle misorientation, which in turn can trigger developmental defects and cancer progression. Little is known about the cellular signaling pathway involved in the misorientation of proliferating cells that evade apoptosis after DNA damage. In this study, we found that perturbations to spindle orientation were induced in ultraviolet C (UVC)-irradiated surviving cells. N-terminal truncated Rho GDP-dissociation inhibitor β (RhoGDIβ), which is produced by UVC irradiation, distorted the spindle orientation of HeLa cells cultured on Matrigel. The short hairpin RNA-mediated knockdown of RhoGDIβ significantly attenuated UVC-induced misorientation. Subsequent expression of wild-type RhoGDIβ, but not a noncleavable mutant, RhoGDIβ (D19A), again led to a relative increase in spindle misorientation in response to UVC. Our findings revealed that RhoGDIβ impacts spindle orientation in response to DNA damage. 相似文献
72.
Siranush Babakhanova Erica E. Jung Kazuhiko Namikawa Hanbin Zhang Yangdong Wang Oksana M. Subach Dmitry A. Korzhenevskiy Tatiana V. Rakitina Xian Xiao Wenjing Wang Jing Shi Mikhail Drobizhev Demian Park Lea Eisenhard Hongyun Tang Reinhard W. Kster Fedor V. Subach Edward S. Boyden Kiryl D. Piatkevich 《Protein science : a publication of the Protein Society》2022,31(3):728
In vivo imaging of model organisms is heavily reliant on fluorescent proteins with high intracellular brightness. Here we describe a practical method for rapid optimization of fluorescent proteins via directed molecular evolution in cultured mammalian cells. Using this method, we were able to perform screening of large gene libraries containing up to 2 × 107 independent random genes of fluorescent proteins expressed in HEK cells, completing one iteration of directed evolution in a course of 8 days. We employed this approach to develop a set of green and near‐infrared fluorescent proteins with enhanced intracellular brightness. The developed near‐infrared fluorescent proteins demonstrated high performance for fluorescent labeling of neurons in culture and in vivo in model organisms such as Caenorhabditis elegans, Drosophila, zebrafish, and mice. Spectral properties of the optimized near‐infrared fluorescent proteins enabled crosstalk‐free multicolor imaging in combination with common green and red fluorescent proteins, as well as dual‐color near‐infrared fluorescence imaging. The described method has a great potential to be adopted by protein engineers due to its simplicity and practicality. We also believe that the new enhanced fluorescent proteins will find wide application for in vivo multicolor imaging of small model organisms. 相似文献
73.
Brbara Della Noce Renato Martins da Silva Marcelle Vianna de Carvalho Uhl Satoru Konnai Kazuhiko Ohashi Christiano Calixto Anglica Arcanjo Leonardo Araujo de Abreu Stephanie Serafim de Carvalho Itabajara da Silva Vaz Jr. Carlos Logullo 《The Journal of biological chemistry》2022,298(3)
Carbohydrate metabolism not only functions in supplying cellular energy but also has an important role in maintaining physiological homeostasis and in preventing oxidative damage caused by reactive oxygen species. Previously, we showed that arthropod embryonic cell lines have high tolerance to H2O2 exposure. Here, we describe that Rhipicephalus microplus tick embryonic cell line (BME26) employs an adaptive glucose metabolism mechanism that confers tolerance to hydrogen peroxide at concentrations too high for other organisms. This adaptive mechanism sustained by glucose metabolism remodeling promotes cell survival and redox balance in BME26 cell line after millimolar H2O2 exposure. The present work shows that this tick cell line could tolerate high H2O2 concentrations by initiating a carbohydrate-related adaptive response. We demonstrate that gluconeogenesis was induced as a compensation strategy that involved, among other molecules, the metabolic enzymes NADP-ICDH, G6PDH, and PEPCK. We also found that this phenomenon was coupled to glycogen accumulation and glucose uptake, supporting the pentose phosphate pathway to sustain NADPH production and leading to cell survival and proliferation. Our findings suggest that the described response is not atypical, being also observed in cancer cells, which highlights the importance of this model to all proliferative cells. We propose that these results will be useful in generating basic biological information to support the development of new strategies for disease treatment and parasite control. 相似文献
74.
Nishida K Yamaguchi O Hirotani S Hikoso S Higuchi Y Watanabe T Takeda T Osuka S Morita T Kondoh G Uno Y Kashiwase K Taniike M Nakai A Matsumura Y Miyazaki J Sudo T Hongo K Kusakari Y Kurihara S Chien KR Takeda J Hori M Otsu K 《Molecular and cellular biology》2004,24(24):10611-10620
The molecular mechanism for the transition from cardiac hypertrophy, an adaptive response to biomechanical stress, to heart failure is poorly understood. The mitogen-activated protein kinase p38alpha is a key component of stress response pathways in various types of cells. In this study, we attempted to explore the in vivo physiological functions of p38alpha in hearts. First, we generated mice with floxed p38alpha alleles and crossbred them with mice expressing the Cre recombinase under the control of the alpha-myosin heavy-chain promoter to obtain cardiac-specific p38alpha knockout mice. These cardiac-specific p38alpha knockout mice were born normally, developed to adulthood, were fertile, exhibited a normal life span, and displayed normal global cardiac structure and function. In response to pressure overload to the left ventricle, they developed significant levels of cardiac hypertrophy, as seen in controls, but also developed cardiac dysfunction and heart dilatation. This abnormal response to pressure overload was accompanied by massive cardiac fibrosis and the appearance of apoptotic cardiomyocytes. These results demonstrate that p38alpha plays a critical role in the cardiomyocyte survival pathway in response to pressure overload, while cardiac hypertrophic growth is unaffected despite its dramatic down-regulation. 相似文献
75.
Ozeki M Watanabe H Luo J Nakano T Takeuchi K Kureishi Y Ito M Nakano T Ohashi K Hayashi H 《Molecular and cellular biochemistry》2004,259(1-2):169-176
The protein kinase Akt participates in such important functions of endothelial cells as nitric oxide production and angiogenesis, activities that involve changes in cytosolic Ca2+ concentration. However, it is not known if activation of Akt is itself involved in the regulation of Ca2+ signals produced in these cells. The objective of this study was to examine if Akt is involved in the regulation of Ca2+ signaling in endothelial cells. Agonist-stimulated Ca2+ signals, assessed using fura-2, were compared in porcine aortic endothelial cells under control conditions or conditions in which Akt was blocked either by different inhibitors of phosphatidylinositol 3-kinase (PI3 kinase)/Akt or by transient expression of a dominant-negative form of Akt (dnAkt). We found that the release of intracellular Ca2+ stores stimulated by bradykinin or thapsigargin is not affected by the PI3 kinase inhibitors LY294002 and wortmannin, or by expression of dnAkt. LY294002 dose-dependently inhibits store-operated Ca2+ entry, an effect not seen with wortmannin. Expression of dnAkt has no effect on store-operated Ca2+ entry. We conclude that Akt is not involved in the regulation of agonist-stimulated Ca2+ signals in endothelial cells. The compound LY294002 inhibits store-operated Ca2+ entry in these cells by a mechanism independent of PI3 kinase/Akt inhibition. 相似文献
76.
PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes 总被引:11,自引:0,他引:11
Here we provide evidence that astrocytes affect neuronal synaptogenesis by the process of adhesion. Local contact with astrocytes via integrin receptors elicited protein kinase C (PKC) activation in individual dissociated neurons cultured in astrocyte-conditioned medium. This activation, initially focal, soon spread throughout the entire neuron. We then demonstrated pharmacologically that the arachidonic acid cascade, triggered by the integrin reception, is responsible for the global activation of PKC. Local astrocytic contact also facilitated excitatory synaptogenesis throughout the neuron, a process which could be blocked by inhibitors of both integrins and PKC. Thus, propagation of PKC signaling represents an underlying mechanism for global neuronal maturation following local astrocyte adhesion. 相似文献
77.
Ihara M Matsuda K Shimomura M Sattelle DB Komai K 《Bioscience, biotechnology, and biochemistry》2004,68(3):761-763
To compare the actions of clothianidin, a neonicotinoid acting on insect nicotinic acetylcholine receptors, and related compounds with that of imidacloprid, the compounds were tested on the Drosophila SAD-chicken beta2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes using two-electrode voltage-clamp electrophysiology. The maximum response of the SAD beta 2 nicotinic receptor to clothianidin was larger than that observed for acetylcholine. Ring breakage of the imidazolidine ring of imidacloprid resulting in the generation of a guanidine group was critical for this super agonist action. 相似文献
78.
79.
Hamada K Nishida T Yamauchi K Fukushima K Kondo R Tsutsumi Y 《Journal of plant research》2004,117(4):303-310
4-Coumarate:coenzyme A (CoA) ligase (4CL, EC 6.2.1.12) in crude enzyme preparation from the developing xylem of black locust (Robinia pseudoacacia) converted sinapate to sinapoyl CoA. The sinapate-converting activity was not inhibited by other cinnamate derivatives, such as p-coumarate, caffeate or ferulate, in the mixed-substrate assay. The crude extract prepared from the developing xylem was separated by anion-exchange chromatography into three different 4CL isoforms. The isoform 4CL1 had a strong substrate preference for p-coumarate, but lacked the activity for ferulate and sinapate. On the other hand, 4CL2 and 4CL3 displayed activity toward sinapate and also possessed high activity toward caffeate as well as p-coumarate. The crude extract from the shoots exhibited a very similar substrate preference to that of the developing xylem; therefore, 4CL2 may be a major isoform in both crude enzyme preparations. These results support the hypothesis that sinapate-converting 4CL isoform is constitutively expressed in lignin-forming cells. 相似文献
80.
Kazuhiko?HOSHIZAKIEmail author Kaoru?NIIYAMA Katsuhiko?KIMURA Tamon?YAMASHITA Yukiko?BEKKU Toshinori?OKUDA Eng Seng?QUAH Nur SUPARDI Md.?Noor 《Ecological Research》2004,19(3):357-363
To clarify consistency in the size of carbon pool of a lowland tropical rainforest, we calculated changes in above-ground biomass in the Pasoh Forest Reserve, Peninsular Malaysia. We estimated the total above-ground biomass of a mature stand using tree census data obtained in a 6-ha plot every 2years from 1994 to 1998. The total above-ground biomass decreased consistently from 1994 (431Mgha–1) to 1998 (403Mgha–1) (1Mg=103 kg). These are much lower than that in 1973 for a 0.2ha portion of the same area, suggesting that the the total above-ground biomass reduction might have been consistent in recent decades. This trend contrasted with a major trend for neotropical forests. During 1994–1998, the forest gained 23.0 and 0.88Mgha–1 of the total above-ground biomass by tree growth and recruitment, respectively, and lost 51.9Mgha–1 by mortality. Overall, the biomass decreased by 28.4Mgha–1 (i.e. 7.10Mgha–1·year–1), which is almost equivalent to losing a 76-cm-diameter living tree per hectare per year. Analysis of positive and negative components of biomass change revealed that deaths of large trees dominated the total above-ground biomass decrease. The forest biomass also varied spatially, with the total above-ground biomass density ranging 212–655Mgha–1 on a 0.2-ha basis (n= 30 subplots, 1998) and 365–440Mgha–1 on a 1ha basis. A large decrease of the total above-ground biomass density (>50Mg per ha per 2years) in several 0.2-ha subplots contributed to the overall decrease in the 6-ha total above-ground biomass. In the present study, we discuss the association between forest dynamics and biomass fluctuation, and the implication for carbon cycling in mature forests with emphasis on forest monitoring and assessments of soil and decomposition systems. 相似文献