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61.
Yukioka F Matsuzaki S Kawamoto K Koyama Y Hitomi J Katayama T Tohyama M 《Neurochemistry international》2008,52(4-5):683-687
In the previous reports, we showed that the familial Alzheimer's disease (AD)-linked presenilin-1 (PS1) mutation induced the fragility to the endoplasmic reticulum (ER) stress and that caspase-4 mediates ER stress-induced- and beta-amyloid induced-apoptotic signaling in human cells. These results suggest the involvement of ER stress and caspase-4 in the cell death observed in AD. In this report, we studied the activation of caspase-4 in the familial AD-linked PS1 mutation (DeltaE9). Cleavage of caspase-4 under ER stress was enhanced by the overexpression of the familial AD-linked mutation (DeltaE9), showing that caspase-4 is a key caspase involved in the apoptotic signaling of AD. We also showed that the overexpression of caspase-4 induced cleavage of caspase-9 and caspase-3 without releasing cytochrome-c from the mitochondria. Thus, caspase-4 activates downstream caspases independently of mitochondrial apoptotic signaling and this might contribute to the pathogenesis of AD. To sum up our data, the familial AD-linked PS1 mutation accelerates the cleavage of caspase-4 under the ER stress and results in the activation of caspase-9 and caspase-3, apoptosis signal, without releasing cytochrome-c. 相似文献
62.
We previously reported that serotonin (5-HT) increased glial cell line-derived neurotrophic factor (GDNF) release in a 5-HT2 receptor (5-HT2 R) and mitogen-activated protein kinase kinase/extracellular signal-related kinase (MEK/ERK)-dependent manner in rat C6 glioma cells (C6 cells), a model of astrocytes. We herein found that 5-HT-induced rapid ERK phosphorylation was blocked by 5-HT2 R antagonists in C6 cells. We therefore examined 5-HT-induced ERK phosphorylation to reveal the mechanism of 5-HT-induced GDNF mRNA expression. As 5-HT-induced ERK phosphorylation was blocked by inhibitors for Gαq/11 and fibroblast growth factor receptor (FGFR), but not for second messengers downstream of Gαq/11 , 5-HT2 R-mediated FGFR transactivation was suggested to be involved in the ERK phosphorylation. Although FGFR1 and 2 were functionally expressed in C6 cells, 5-HT selectively phosphorylated FGFR2. Indeed, small interfering RNA for FGFR2, but not for FGFR1, blocked 5-HT-induced ERK phosphorylation. As Src family tyrosine kinase inhibitors and microtubule depolymerizing agents blocked 5-HT-induced FGFR2 phosphorylation, Src family tyrosine kinase and stabilized microtubules were suggested to act upstream of FGFR2. Finally, 5-HT-induced GDNF mRNA expression was also inhibited by the blockade of 5-HT2 R, FGFR, and Src family tyrosine kinase. In conclusion, our findings suggest that 5-HT induces GDNF mRNA expression via 5-HT2 R-mediated FGFR2 transactivation in C6 cells. 相似文献
63.
Physiological properties of rod photoreceptor cells in green-sensitive cone pigment knock-in mice 下载免费PDF全文
Sakurai K Onishi A Imai H Chisaka O Ueda Y Usukura J Nakatani K Shichida Y 《The Journal of general physiology》2007,130(1):21-40
Rod and cone photoreceptor cells that are responsible for scotopic and photopic vision, respectively, exhibit photoresponses different from each other and contain similar phototransduction proteins with distinctive molecular properties. To investigate the contribution of the different molecular properties of visual pigments to the responses of the photoreceptor cells, we have generated knock-in mice in which rod visual pigment (rhodopsin) was replaced with mouse green-sensitive cone visual pigment (mouse green). The mouse green was successfully transported to the rod outer segments, though the expression of mouse green in homozygous retina was approximately 11% of rhodopsin in wild-type retina. Single-cell recordings of wild-type and homozygous rods suggested that the flash sensitivity and the single-photon responses from mouse green were three to fourfold lower than those from rhodopsin after correction for the differences in cell volume and levels of several signal transduction proteins. Subsequent measurements using heterozygous rods expressing both mouse green and rhodopsin E122Q mutant, where these pigments in the same rod cells can be selectively irradiated due to their distinctive absorption maxima, clearly showed that the photoresponse of mouse green was threefold lower than that of rhodopsin. Noise analysis indicated that the rate of thermal activations of mouse green was 1.7 x 10(-7) s(-1), about 860-fold higher than that of rhodopsin. The increase in thermal activation of mouse green relative to that of rhodopsin results in only 4% reduction of rod photosensitivity for bright lights, but would instead be expected to severely affect the visual threshold under dim-light conditions. Therefore, the abilities of rhodopsin to generate a large single photon response and to retain high thermal stability in darkness are factors that have been necessary for the evolution of scotopic vision. 相似文献
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65.
Ohara Chisato Sekiguchi Atsushi Takakura Shu Endo Yuka Tamura Naho Kikuchi Hiroe Maruo Kazushi Sugawara Norio Hatano Kenji Kawanishi Hitomi Funaba Misako Sugawara Ayako Nohara Nobuhiro Kawai Keisuke Fukudo Shin Sudo Nobuyuki Cooper Zafra Yoshiuchi Kazuhiro Ando Tetsuya 《BioPsychoSocial medicine》2020,14(1):1-3
Although fatigue is a common and distressing symptom in cancer survivors, the mechanism of fatigue is not fully understood. Therefore, this study aims to investigate the relation between the fatigue and mindfulness of breast cancer survivors using anxiety, depression, pain, loneliness, and sleep disturbance as mediators. Path analysis was performed to examine direct and indirect associations between mindfulness and fatigue. Participants were breast cancer survivors who visited a breast surgery department at a university hospital in Japan for hormonal therapy or regular check-ups after treatment. The questionnaire measured cancer-related-fatigue, mindfulness, anxiety, depression, pain, loneliness, and sleep disturbance. Demographic and clinical characteristics were collected from medical records. Two-hundred and seventy-nine breast cancer survivors were registered, of which 259 answered the questionnaire. Ten respondents with incomplete questionnaire data were excluded, resulting in 249 participants for the analyses. Our final model fit the data well (goodness of fit index = .993; adjusted goodness of fit index = .966; comparative fit index = .999; root mean square error of approximation = .016). Mindfulness, anxiety, depression, pain, loneliness, and sleep disturbance were related to fatigue, and mindfulness had the most influence on fatigue (β = − .52). Mindfulness affected fatigue not only directly but also indirectly through anxiety, depression, pain, loneliness, and sleep disturbance. The study model helps to explain the process by which mindfulness affects fatigue. Our results suggest that mindfulness has both direct and indirect effects on the fatigue of breast cancer survivors and that mindfulness can be used to more effectively reduce their fatigue. It also suggests that health care professionals should be aware of factors such as anxiety, depression, pain, loneliness, and sleep disturbance in their care for fatigue of breast cancer survivors. This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN number. 000027720) on June 12, 2017. 相似文献
66.
Chen Chong-Juan Liu Xue-Yan Wang Xian-Wei Hu Chao-Chen Xu Shi-Qi Mao Rong Bu Zhao-Jun Fang Yun-Ting Koba Keisuke 《Plant and Soil》2021,467(1-2):345-357
Plant and Soil - Plant carbon (C), nitrogen (N), phosphorus (P) levels and their stoichiometry and N uptake strategies are important aspects influencing vegetation composition and C dynamics in... 相似文献
67.
Oluyomi Stephen Adeyemi Nthatisi Innocentia Molefe-Nyembe Abiodun Omokehinde Eseola Winfried Plass Oluwatosin Kudirat Shittu Ibrahim Olatunji Yunusa Olubunmi Atolani Ikponmwosa Owen Evbuomwan Oluwakemi J. Awakan Keisuke Suganuma Kentaro Kato 《The Yale journal of biology and medicine》2021,94(2):199
The Trypanosoma spp. cause animal and human trypanosomiasis characterized with appreciable health and economic burden mostly in developing nations. There is currently no effective therapy for this parasitic disease, due to poor drug efficacy, drug resistance, and unwanted toxicity, etc. Therefore, new anti-Trypanosoma agents are urgently needed. This study explored new series of imidazoles for anti-Trypanosoma properties in vitro and in vivo. The imidazoles showed moderate to strong and specific action against growth of T. congolense. For example, the efficacy of the imidazole compounds to restrict Trypanosoma growth in vitro was ≥ 12-fold specific towards T. congolense relative to the mammalian cells. Additionally, the in vivo study revealed that the imidazoles exhibited promising anti-Trypanosoma efficacy corroborating the in vitro anti-parasite capacity. In particular, three imidazole compounds (C1, C6, and C8) not only cleared the systemic parasite burden but cured infected rats after no death was recorded. On the other hand, the remaining five imidazole compounds (C2, C3, C4, C5, and C7) drastically reduced the systemic parasite load while extending survival time of the infected rats by 14 days as compared with control. Untreated control died 3 days post-infection, while the rats treated with diminazene aceturate were cured comparable to the results obtained for C1, C6, and C8. In conclusion, this is the first study demonstrating the potential of these new series of imidazoles to clear the systemic parasite burden in infected rats. Furthermore, a high selectivity index of imidazoles towards T. congolense in vitro and the oral LD50 in rats support anti-parasite specific action. Together, findings support the anti-parasitic prospects of the new series of imidazole derivatives. 相似文献
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69.
Aida Rieko Hagiwara Keitaro Okano Kazunori Nakata Kyoko Obata Yuho Yamashita Takahiro Yoshida Kaoru Hagiwara Hiromi 《Molecular biology reports》2021,48(3):2291-2297
Molecular Biology Reports - Apigenin is a flavonoid with antioxidant and anticancer effects. It has been reported that apigenin inhibits proliferation, migration, and invasion and induces apoptosis... 相似文献
70.
Huaxin Yu Tasuku Hamaguchi Yoshiki Nakajima Koji Kato Keisuke Kawakami Fusamichi Akita Koji Yonekura Jian-Ren Shen 《BBA》2021,1862(10):148471
Photosystem II (PSII) functions mainly as a dimer to catalyze the light energy conversion and water oxidation reactions. However, monomeric PSII also exists and functions in vivo in some cases. The crystal structure of monomeric PSII has been solved at 3.6 Å resolution, but it is still not clear which factors contribute to the formation of the dimer. Here, we solved the structure of PSII monomer at a resolution of 2.78 Å using cryo-electron microscopy (cryo-EM). From our cryo-EM density map, we observed apparent differences in pigments and lipids in the monomer-monomer interface between the PSII monomer and dimer. One β-carotene and two sulfoquinovosyl diacylglycerol (SQDG) molecules are found in the monomer-monomer interface of the dimer structure but not in the present monomer structure, although some SQDG and other lipid molecules are found in the analogous region of the low-resolution crystal structure of the monomer, or cryo-EM structure of an apo-PSII monomer lacking the extrinsic proteins from Synechocystis sp. PCC 6803. In the current monomer structure, a large part of the PsbO subunit was also found to be disordered. These results indicate the importance of the β-carotene, SQDG and PsbO in formation of the PSII dimer. 相似文献