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81.
Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury
Obata K Katsura H Miyoshi K Kondo T Yamanaka H Kobayashi K Dai Y Fukuoka T Akira S Noguchi K 《Journal of neurochemistry》2008,105(6):2249-2259
Toll-like receptors (TLRs) play an essential role in innate immune responses and in the initiation of adaptive immune responses. Microglia, the resident innate immune cells in the CNS, express TLRs. In this study, we show that TLR3 is crucial for spinal cord glial activation and tactile allodynia after peripheral nerve injury. Intrathecal administration of TLR3 antisense oligodeoxynucleotide suppressed nerve injury-induced tactile allodynia, and decreased the phosphorylation of p38 mitogen-activated protein kinase, but not extracellular signal-regulated protein kinases 1/2, in spinal glial cells. Antisense knockdown of TLR3 also attenuated the activation of spinal microglia, but not astrocytes, caused by nerve injury. Furthermore, down-regulation of TLR3 inhibited nerve injury-induced up-regulation of spinal pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Conversely, intrathecal injection of the TLR3 agonist polyinosine–polycytidylic acid induced behavioral, morphological, and biochemical changes similar to those observed after nerve injury. Indeed, TLR3-deficient mice did not develop tactile allodynia after nerve injury or polyinosine–polycytidylic acid injection. Our results indicate that TLR3 has a substantial role in the activation of spinal glial cells and the development of tactile allodynia after nerve injury. Thus, blocking TLR3 in the spinal glial cells might provide a fruitful strategy for treating neuropathic pain. 相似文献
82.
Siddiqui MA Yamanaka A Hirooka K Bamaba T Kobayashi A Imanaka T Fukusaki E Fujiwara S 《Biochemical and biophysical research communications》2005,331(4):1127-1136
Enzymatic and thermodynamic characteristics of type II isopentenyl diphosphate (IPP):dimethylallyl diphosphate (DMAPP) isomerase (Tk-IDI) from Thermococcus kodakaraensis, which catalyzes the interconversion of IPP and DMAPP, were examined. FMN was tightly bound to Tk-IDI, and the enzyme required NADPH and Mg2+ for the isomerization in both directions. The melting temperature (Tm), the change of enthalpy (deltaH(m)), and the heat capacity change (deltaC(p)) of Tk-IDI were 88.0 degrees C, 444 kJ mol(-1), and 13.2 kJ mol(-1) K(-1), respectively, indicating that Tk-IDI is fairly thermostable. Kinetic parameters dramatically changed when the temperature crossed 80 degrees C even though its native overall structure was stably maintained up to 90 degrees C, suggesting that local conformational change would occur around 80 degrees C. This speculation was supported by the result of the circular dichroism analysis that showed the shift of the alpha-helical content occurred at 80 degrees C. 相似文献
83.
Suzuki T Kanai Y Hara T Sasaki J Sasaki T Kohara M Maehama T Taya C Shitara H Yonekawa H Frohman MA Yokozeki T Kanaho Y 《Molecular and cellular biology》2006,26(16):6149-6156
The mammalian small GTPase ADP-ribosylation factor 6 (ARF6) plays important roles in a wide variety of cellular events, including endocytosis, actin cytoskeletal reorganization, and phosphoinositide metabolism. However, physiological functions for ARF6 have not previously been examined. Here, we described the consequence of ARF6 ablation in mice, which manifests most obviously in the context of liver development. Livers from ARF6-/- embryos are smaller and exhibit hypocellularity, due to the onset of midgestational liver cell apoptosis. Preceding the apoptosis, however, defective hepatic cord formation is observed; the liver cells migrate abnormally upon exiting the primordial hepatic epithelial sheet and clump rather than becoming dispersed. Consistent with this observation, the ability of hepatocyte growth factor/scatter factor (HGF) to induce hepatic cord-like structures from ARF6-/- fetal hepatocytes cultured in vitro in collagen gel matrix is impaired. Finally, we show that endogenous ARF6 in wild-type fetal hepatocytes is activated in response to HGF stimulation. These results provide evidence that ARF6 is an essential component in the signaling pathway coupling HGF signaling to hepatic cord formation. 相似文献
84.
Keiichi Yamanaka Takehisa Nakanishi Hiromitsu Saito Junko Maruyama Kenichi Isoda Ayumu Yokochi Kyoko Imanaka-Yoshida Kenshiro Tsuda Masato Kakeda Ryuji Okamoto Satoshi Fujita Yoichiro Iwakura Noboru Suzuki Masaaki Ito Kazuo Maruyama Esteban C. Gabazza Toshimichi Yoshida Motomu Shimaoka Hitoshi Mizutani 《PloS one》2014,9(8)
The skin is an immune organ that contains innate and acquired immune systems and thus is able to respond to exogenous stimuli producing large amount of proinflammatory cytokines including IL-1 and IL-1 family members. The role of the epidermal IL-1 is not limited to initiation of local inflammatory responses, but also to induction of systemic inflammation. However, association of persistent release of IL-1 family members from severe skin inflammatory diseases such as psoriasis, epidermolysis bullosa, atopic dermatitis, blistering diseases and desmoglein-1 deficiency syndrome with diseases in systemic organs have not been so far assessed. Here, we showed the occurrence of severe systemic cardiovascular diseases and metabolic abnormalities including aberrant vascular wall remodeling with aortic stenosis, cardiomegaly, impaired limb and tail circulation, fatty tissue loss and systemic amyloid deposition in multiple organs with liver and kidney dysfunction in mouse models with severe dermatitis caused by persistent release of IL-1s from the skin. These morbid conditions were ameliorated by simultaneous administration of anti-IL-1α and IL-1β antibodies. These findings may explain the morbid association of arteriosclerosis, heart involvement, amyloidosis and cachexia in severe systemic skin diseases and systemic autoinflammatory diseases, and support the value of anti-IL-1 therapy for systemic inflammatory diseases. 相似文献
85.
Induced pluripotent stem cells: past, present, and future 总被引:1,自引:0,他引:1
Yamanaka S 《Cell Stem Cell》2012,10(6):678-684
The development of iPSCs reflected the merging of three major scientific streams and has in turn led to additional new branches of investigation. However, there is still debate about whether iPSCs are functionally equivalent to ESCs. This question should be answered only by science, not by politics or business. 相似文献
86.
Ken-ichi Itoh Kaoru Nakamura Tadashi Aoyama Ryusuke Matsuba Tsuyoshi Kakimoto Masahiko Murakami Rio Yamanaka Toshiya Muranaka Hiroshi Sakamaki Toshio Takido 《Biotechnology letters》2012,34(11):2083-2086
Aromatic ketones were reduced using suspension culture of Chlorella sp. MK201 under fluorescent light illumination producing the corresponding chiral alcohols in high yields with excellent enantiomeric excess (ee). For example, 2′,3′,4′,5′,6′-pentafluoroacetophenone at 0.25?mg/ml was converted to the corresponding (S)-alcohol in 80?% yield with?>99?% ee by 1?mg dry wt of Chlorella/ml in 12?h illumination (2,000 lux). 相似文献
87.
Yamaguchi T Ishii K Yamanaka M Yasuda K 《Journal of strength and conditioning research / National Strength & Conditioning Association》2006,20(4):804-810
The purpose of the present study was to clarify the effect of static stretching on muscular performance during concentric isotonic (dynamic constant external resistance [DCER]) muscle actions under various loads. Concentric DCER leg extension power outputs were assessed in 12 healthy male subjects after 2 types of pretreatment. The pretreatments included (a) static stretching treatment performing 6 types of static stretching on leg extensors (4 sets of 30 seconds each with 20-second rest periods; total duration 20 minutes) and (b) nonstretching treatment by resting for 20 minutes in a sitting position. Loads during assessment of the power output were set to 5, 30, and 60% of the maximum voluntary contractile (MVC) torque with isometric leg extension in each subject. The peak power output following the static stretching treatment was significantly (p < 0.05) lower than that following the nonstretching treatment under each load (5% MVC, 418.0 +/- 82.2 W vs. 466.2 +/- 89.5 W; 30% MVC, 506.4 +/- 82.8 W vs. 536.4 +/- 97.0 W; 60% MVC, 478.6 +/- 77.5 W vs. 523.8 +/- 97.8 W). The present study demonstrated that relatively extensive static stretching significantly reduces power output with concentric DCER muscle actions under various loads. Common power activities are carried out by DCER muscle actions under various loads. Therefore, the result of the present study suggests that relatively extensive static stretching decreases power performance. 相似文献
88.
Kohno T Ichikawa H Totoki Y Yasuda K Hiramoto M Nammo T Sakamoto H Tsuta K Furuta K Shimada Y Iwakawa R Ogiwara H Oike T Enari M Schetter AJ Okayama H Haugen A Skaug V Chiku S Yamanaka I Arai Y Watanabe S Sekine I Ogawa S Harris CC Tsuda H Yoshida T Yokota J Shibata T 《Nature medicine》2012,18(3):375-377
89.
Satoi Nagasawa Anna S. Sedukhina Yuko Nakagawa Ichiro Maeda Manabu Kubota Shigeko Ohnuma Koichiro Tsugawa Tomohiko Ohta Marta Roche-Molina Juan A. Bernal Ana J. Narváez Anand D. Jeyasekharan Ko Sato 《PloS one》2015,10(2)
LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1. 相似文献
90.