http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Tmem64 Modulates Calcium Signaling during RANKL-Mediated Osteoclast Differentiation
Kim, H.,Kim, T.,Jeong, B.C.,Cho, I.T.,Han, D.,Takegahara, N.,Negishi-Koga, T.,Takayanagi, H.,Lee, J.,Sul, J.Y.,Prasad, V.,Lee, S.,Choi, Y. Cell Press 2013 Cell metabolism Vol.17 No.2
Osteoclast maturation and function primarily depend on receptor activator of NF-κB ligand (RANKL)-mediated induction of nuclear factor of activated T cells c1 (NFATc1), which is further activated via increased intracellular calcium ([Ca<SUP>2+</SUP>]<SUB>i</SUB>) oscillation. However, the coordination mechanism that mediates Ca<SUP>2+</SUP> oscillation during osteoclastogenesis remains ill defined. Here, we identified transmembrane protein 64 (Tmem64) as a regulator of Ca<SUP>2+</SUP> oscillation during osteoclastogenesis. We found that Tmem64-deficient mice exhibit increased bone mass due in part to impaired osteoclast formation. Using in vitro osteoclast culture systems, we show here that Tmem64 interacts with sarcoplasmic endoplasmic reticulum Ca<SUP>2+</SUP> ATPase 2 (SERCA2) and modulates its activity. Consequently, Tmem64 deficiency significantly diminishes RANKL-induced [Ca<SUP>2+</SUP>]<SUB>i</SUB> oscillation, which results in reduced Ca<SUP>2+</SUP>/calmodulin-dependent protein kinases (CaMK) IV and mitochondrial ROS, both of which contribute to achieving the CREB activity necessary for osteoclast formation. These data demonstrate that Tmem64 is a positive modulator of osteoclast differentiation via SERCA2-dependent Ca<SUP>2+</SUP> signaling.
Identification of an Adenylyl Cyclase Inhibitor for Treating Neuropathic and Inflammatory Pain
Wang, H.,Xu, H.,Wu, L.-J.,Kim, S. S.,Chen, T.,Koga, K.,Descalzi, G.,Gong, B.,Vadakkan, K. I.,Zhang, X.,Kaang, B.-K.,Zhuo, M. American Association for the Advancement of Scienc 2011 Science Translational Medicine Vol.3 No.65
<P>Neuropathic pain, often caused by nerve injury, is commonly observed among patients with different diseases. Because its basic mechanisms are poorly understood, effective medications are limited. Previous investigations of basic pain mechanisms and drug discovery efforts have focused mainly on early sensory neurons such as dorsal root ganglion and spinal dorsal horn neurons, and few synaptic-level studies or new drugs are designed to target the injury-related cortical plasticity that accompanies neuropathic pain. Our previous work has demonstrated that calcium-stimulated adenylyl cyclase 1 (AC1) is critical for nerve injury-induced synaptic changes in the anterior cingulate cortex. Through rational drug design and chemical screening, we have identified a lead candidate AC1 inhibitor, NB001, which is relatively selective for AC1 over other adenylate cyclase isoforms. Using a variety of behavioral tests and toxicity studies, we have found that NB001, when administered intraperitoneally or orally, has an analgesic effect in animal models of neuropathic pain, without any apparent side effects. Our study thus shows that AC1 could be a productive therapeutic target for neuropathic pain and describes a new agent for the possible treatment of neuropathic pain.</P>
Koga, K.,Descalzi, G.,Chen, T.,Ko, H.G.,Lu, J.,Li, S.,Son, J.,Kim, T.,Kwak, C.,Huganir, Richard L.,Zhao, M.g.,Kaang, B.K.,Collingridge, Graham L.,Zhuo, M. Cell Press 2015 Neuron Vol.85 No.2
Chronic pain can lead to anxiety and anxiety can enhance the sensation of pain.@?Unfortunately, little is known about the synaptic mechanisms that mediate these re-enforcing interactions. Here we characterized two forms of long-term potentiation (LTP) in the anterior cingulate cortex (ACC); a presynaptic form (pre-LTP) that requires kainate receptors and a postsynaptic form (post-LTP) that requires N-methyl-D-aspartate receptors. Pre-LTP also involves adenylyl cyclase and protein kinase A and is expressed via a mechanism involving hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Interestingly, chronic pain and anxiety both result in selective occlusion of pre-LTP. Significantly, microinjection of the HCN blocker ZD7288 into the ACC in vivo produces both anxiolytic and analgesic effects. Our results provide a mechanism by which two forms of LTP in the ACC may converge to mediate the interaction between anxiety and chronic pain.
Koga, A.,Kurata, K.,Ohata, K.,Nakajima, M.,Hirose, H.,Furukawa, R.,Kanai, Y.,Chikamune, T. Asian Australasian Association of Animal Productio 1999 Animal Bioscience Vol.12 No.6
From previous studies, there is a strong possibility in buffaloes that the marked increase in blood volume (BV) under hot conditions contributes to heat transportation from the rectum to the skin. The present study was done to clarify changes with environmental temperature on water-shift between blood and extracellular fluid (ECF), heat distribution between the rectum and the skin, and blood flow rates (BFR) at the hind legs (reflecting the skin surface). Four buffaloes and four Friesian cows were successively exposed to three different temperatures of $20^{\circ}C$, $30^{\circ}C$ and $35^{\circ}C$. BV and ECF volume were measured with Evans' blue and sodium-thiocyanate dilution methods, respectively. Rectal and subcutaneous (as the skin) temperatures were measured by copper-constantan thermocouples. BFR were measured by a supersonic blood flow meter. With an increase in environmental temperature, skin temperature in buffaloes increased significantly than cows, but rectal temperature was not significantly different between two species. BV, especially plasma compartment, increased significantly in only buffaloes, while ECF volume did not change in both species. BFR increased significantly in buffaloes, but not in cows. From these results, the increased of BV may be caused by water flowing from ECF compartment. The water-shift may induce the increase of BFR and skin temperature. It is suggested in the present study that internal changes of blood compartment in buffaloes contribute to transfer of heat to the skin surface.
Flavobacterium meningosepticum 이 생산하는 peroxidase 의 분리정제 및 특성
양한철,최양문,Koga, S,Shimizu, S,Yamada, H 한국농화학회 1991 Applied Biological Chemistry (Appl Biol Chem) Vol.34 No.4
Peroxidase는 식물체에 널리 분포되어 있으며, 특히 horseradish에 많이 존재하고 있으나 미생물로부터 peroxidase의 생산은 거의 알려져 있지 않다. 토양으로부터 peroxidase를 생산하는 F, meningoseptium을 분리하였으며 분리균이 생산하는 intracellular enzyme을 DEAE-sephacel, phenyl-Sepharose CL-4B, Sephacryl S-300을 거쳐 효소를 분리 정제하여 효소의 특성을 검토하였다. Peroxidase의 native molecular weight는 220,000이며, subunit의 M.W.은 54,000으로 추정되었다. 본 효소는 pH 5.0-7.0, 50℃ 이하의 온도에서 안정성을 나타내었다.
Koo, Jaseung,Koga, Tadanori,Li, Bingquan,Satija, Sushil K.,Rafailovich, Miriam H. American Chemical Society 2016 Macromolecules Vol.49 No.9
<P>We investigated the effect of density fluctuation of supercritical carbon dioxide (scCO(2)) on anomalous swelling of multilayer polymer thin films On the ridge in the pressure temperature phase diagram of CO2. In order to measure the swelling ratio along the film depth, we alternatively deposited hydrogenated poly(methyl Methacrylate) (PMMA) and deuterated polystyrene (dPS) thin films and performed the neutron reflectivity measurements as a function of CO2 pressure at 36 degrees C. The results showed that, in contrast to previous studies, CO2 was to penetrate deeply:throughout the, multilayer thin film where the magnitude of swelling along the density fluctuation ridge of CO2 was independent of film thickness. Block copolymer thin films of dPS-b-PMMA with a parallel lamellar orientation also showed similar swelling behavior in scCO(2). However, it is well-known that single-layer polymer thin films exhibit anomalous swelling behavior only the film surface. This difference is probably due to the fact that the multilayer thin films have the CO2-philic PMMA layer sandwiched between dPS layers, which can function, as a CO2 reservoir, thereby transferring the CO2 molecules from the PMMA layers to the adjacent dPS layers. Furthermore, we found that the interaction between polymers and substrates was not significant in scCO(2) from diffusion dynamics results using neutron reflectivity, thereby facilitating anomalous dilation of polymers near the substrates without a pinning effect.</P>
Alleviating Neuropathic Pain Hypersensitivity by Inhibiting PKM in the Anterior Cingulate Cortex
Li, X.-Y.,Ko, H.-G.,Chen, T.,Descalzi, G.,Koga, K.,Wang, H.,Kim, S. S.,Shang, Y.,Kwak, C.,Park, S.-W.,Shim, J.,Lee, K.,Collingridge, G. L.,Kaang, B.-K.,Zhuo, M. American Association for the Advancement of Scienc 2010 Science Vol.330 No.6009
<P>Synaptic plasticity is a key mechanism for chronic pain. It occurs at different levels of the central nervous system, including spinal cord and cortex. Studies have mainly focused on signaling proteins that trigger these plastic changes, whereas few have addressed the maintenance of plastic changes related to chronic pain. We found that protein kinase M zeta (PKM관) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC). Peripheral nerve injury caused activation of PKM관 in the ACC, and inhibiting PKM관 by a selective inhibitor, 관-pseudosubstrate inhibitory peptide (ZIP), erased synaptic potentiation. Microinjection of ZIP into the ACC blocked behavioral sensitization. These results suggest that PKM관 in the ACC acts to maintain neuropathic pain. PKM관 could thus be a new therapeutic target for treating chronic pain.</P>