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41.
Ryunosuke Ohkawa Hann Low Nigora Mukhamedova Ying Fu Shao-Jui Lai Mai Sasaoka Ayuko Hara Azusa Yamazaki Takahiro Kameda Yuna Horiuchi Peter J. Meikle Gerard Pernes Graeme Lancaster Michael Ditiatkovski Paul Nestel Boris Vaisman Denis Sviridov Andrew Murphy Alan T. Remaley Dmitri Sviridov Minoru Tozuka 《Journal of lipid research》2020,61(12):1577
Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1+/+ and Abca1−/− mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain. 相似文献
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Mai Sakai Tadamichi Morisaka Mari Iwasaki Yayoi Yoshida Ikuo Wakabayashi Atsushi Seko Masahiko Kasamatsu Shiro Kohshima 《Journal of Ethology》2013,31(3):305-313
Mother–calf interactions and the behaviors of mothers during separation from their calves were examined in four Commerson’s dolphin (Cephalorhynchus commersonii) mother–calf pairs. Four infants were observed: 56.8 h over 30 days from birth to 263 days of age, 36.9 h over 20 days from birth to 149 days of age, 10.4 h over 3 days from birth to 2 days of age, and 15.0 h over 3 days from birth to 2 days of age. All four pairs shared common characteristics in the rate and frequencies of mother–calf interactions and the behaviors of mothers during the first week of life. After the first week, individual differences in changes in the frequency of each behavior were observed. The three behaviors considered representative of maternal care (parallel swimming, synchronous breathing, and body-to-body contact) were frequently performed in the first week; thereafter, the frequencies declined. Separate behaviors of mothers were infrequent during the first week and increased with an increase in infants’ age. Bumping by infants increased with time, suggesting an increase in soliciting by calves and conflict between mothers and calves. The frequency of flipper-to-body rubbing also changed but in a complex manner, probably because the calves needed to learn how to perform this behavior from their mothers and because initiator and recipient of this behavior can be changed quickly. 相似文献
44.
The phycobilisome (PBS) is an extra-membrane supramolecular complex composed of many chromophore (bilin)-binding proteins (phycobiliproteins) and linker proteins, which generally are colorless. PBS collects light energy of a wide range of wavelengths, funnels it to the central core, and then transfers it to photosystems. Although phycobiliproteins are evolutionarily related to each other, the binding of different bilin pigments ensures the ability to collect energy over a wide range of wavelengths. Spatial arrangement and functional tuning of the different phycobiliproteins, which are mediated primarily by linker proteins, yield PBS that is efficient and versatile light-harvesting systems. In this review, we discuss the functional and spatial tuning of phycobiliproteins with a focus on linker proteins. 相似文献
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Shinnosuke Machida Mai Tsubamoto Nobuo Kato Kazuo Harada Junko Ohkanda 《Bioorganic & medicinal chemistry》2013,21(14):4004-4010
Bivalent enzyme inhibitors, in which a surface binding module is linked to an active site binding module through a spacer, are a robust approach for site-selectively delivering a minimally-sized agent to a protein surface to regulate its functions, such as protein–protein interactions (PPIs). Previous research revealed that these agents effectively disrupt the interaction between farnesyltransferase (FTase) and the C-terminal region of K-Ras4B protein. However, the whole cell activity of these peptide-based agents is limited due to their low membrane permeability. In this study, we tested a peptidomimetic modification of these bivalent agents using a previously developed inhibitor, FTI-249, and evaluated their cell permeability and biological activity in cells. Confocal cell imaging using fluorescently-labeled agents showed that the peptidomimetic 3-BODIPY penetrated cells, while the peptide-based 1-BODIPY did not. Cell-based evaluation demonstrated that peptidomimetic 3 at a concentration of 100 μM inhibited HDJ-2 processing in cells, indicating that this peptidomimetic modification improves cell permeability, thus leading to enhanced whole cell activity of the bivalent compounds. 相似文献
47.
Caroline Michot Asmaa Mamoune Joseph Vamecq Mai Thao Viou Lu-Sheng Hsieh Eric Testet Jeanne Lainé Laurence Hubert Anne-Frédérique Dessein Monique Fontaine Chris Ottolenghi Laetitia Fouillen Karim Nadra Etienne Blanc Jean Bastin Sophie Candon Mario Pende Arnold Munnich Pascale de Lonlay 《生物化学与生物物理学报:疾病的分子基础》2013,1832(12):2103-2114
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Yan Zhen Yanfen Ye Xiaoli Yu Chunping Mai Ying Zhou Yan Chen Huiling Yang Xiaoming Lyu Ye Song Qiangyun Wu Qiaofen Fu Mengyang Zhao Shengni Hua Hao Wang Zhen Liu Yajie Zhang Weiyi Fang 《PloS one》2013,8(6)
Background
The role of CTGF varies in different types of cancer. The purpose of this study is to investigate the involvement of CTGF in tumor progression and prognosis of human nasopharyngeal carcinoma (NPC).Experimental design
CTGF expression levels were examined in NPC tissues and cells, nasopharynx (NP) tissues, and NP69 cells. The effects and molecular mechanisms of CTGF expression on cell proliferation, migration, invasion, and cell cycle were also explored.Results
NPC cells exhibited decreased mRNA expression of CTGF compared to immortalized human nasopharyngeal epithelial cell line NP69. Similarly, CTGF was observed to be downregulated in NPC compared to normal tissues at mRNA and protein levels. Furthermore, reduced CTGF was negatively associated with the progression of NPC. Knocking down CTGF expression enhanced the colony formation, cell migration, invasion, and G1/S cell cycle transition. Mechanistic analysis revealed that CTGF suppression activated FAK/PI3K/AKT and its downstream signals regulating the cell cycle, epithelial-mesenchymal transition (EMT) and MMPs. Finally, DNA methylation microarray revealed a lack of hypermethylation at the CTGF promoter, suggesting other mechanisms are associated with suppression of CTGF in NPC.Conclusion
Our study demonstrates that reduced expression of CTGF promoted cell proliferation, migration, invasion and cell cycle progression through FAK/PI3K/AKT, EMT and MMP pathways in NPC. 相似文献50.
Karina D. Thielsen Jakob M. Moser Thomas Schmitt-John Morten S. Jensen Kimmo Jensen Mai Marie Holm 《PloS one》2013,8(12)
Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. It is a fatal degenerative disease, best recognized for its debilitating neuromuscular effects. ALS however also induces cognitive impairments in as many as 50% of affected individuals. Moreover, many ALS patients demonstrate cortical hyperexcitability, which has been shown to precede the onset of clinical symptoms. The wobbler mouse is a model of ALS, and like ALS patients the wobbler mouse displays cortical hyperexcitability. Here we investigated if the neocortical aberrations of the wobbler mouse also occur in the hippocampus. Consequently, we performed extracellular field excitatory postsynaptic potential recordings in the CA1 region of the hippocampus on acute brain slices from symptomatic (P45-P60) and presymptomatic (P17-P21) wobbler mice. Significant increased excitation of hippocampal synapses was revealed by leftward shifted input/output-curves in both symptomatic and presymptomatic wobbler mice, and substantiated by population spike occurrence analyses, demonstrating that the increased synaptic excitation precedes the onset of visible phenotypic symptoms in the mouse. Synaptic facilitation tested by paired-pulse facilitation and trains in wobbler and control mice showed no differences, suggesting the absence of presynaptic defects. Immunohistochemical staining revealed that symptomatic wobbler mice have a lower number of parvalbumin positive interneurons when compared to controls and presymptomatic mice. This study reveals that the wobbler mouse model of ALS exhibits hippocampal hyperexcitability. We suggest that the hyperexcitability could be caused by increased excitatory synaptic transmission and a concomitant reduced inhibition due to a decreased number of parvalbumin positive interneurons. Thus we substantiate that wobbler brain impairments are not confined to the motor cortex, but extend to the hippocampus. Importantly, we have revealed more details of the early pathophysiology in asymptomatic animals, and studies like the present may facilitate the development of novel treatment strategies for earlier intervention in ALS patients in the future. 相似文献