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Regulation of Inflammasome Signaling and Its Potential Link to Metabolic Disorders
( Je-wook Yu ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Inflammasome is a cytosolic multiprotein complex to activate caspase-1 leading to the subsequent processing of inactive pro-interleukin- 1-beta (Pro-IL-1) or pro-interleukin-18 (Pro-IL-18) into their active matured form. Inflammasome complex is assembled and activated only upon sensing of pathogen-associated molecular pattern (PAMP) derived from microbial infections or danger- associated molecular pattern (DAMP) derived from tissue injury. Once assembled, inflammasome complex plays a key role in innate immune defense against invading pathogens, but accumulating evidences also suggest that deregulation of inflammasome signaling contributes to the pathogenesis of many metabolic or neurodegerative disorders including type 2 diabetes, obesity, atherosclerosis and Alzheimer’s disease. In this regard, the regulation of inflammasome signaling is of particular interest. Nod-like receptor family, pyrin domain containing 3 (NLRP3) is the best-studied inflammasome component, but it is still poorly understood how NLRP3 inflammasome is assembled and activated in response to a wide range of stimulations. Recently, the role of mitochondria has been increasingly suggested to modulate the activation of NLRP3 inflammasome. Here, we briefly summarize how the NLRP3 inflammasome contributes to the pathogenesis of metabolic or neurodegenerative disorders and how the mitochondria and its related intracellular organelles modulate the activation of NLRP3 inflammmasome.
Yu, Je-Wook,Farias, Andrew,Hwang, Inhwa,Fernandes-Alnemri, Teresa,Alnemri, Emad S. American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.16
<P>Human pyrin with gain-of-function mutations in its B30.2/SPRY domain causes the autoinflammatory disease familial Mediterranean fever by assembling an ASC-dependent inflammasome that activates caspase-1. Wild-type human pyrin can also form an inflammasome complex with ASC after engagement by autoinflammatory PSTPIP1 mutants. How the pyrin inflammasome is activated in the absence of disease-associated mutations is not yet known. We report here that ribotoxic stress triggers the assembly of the human pyrin inflammasome, leading to ASC oligomerization and caspase-1 activation in THP-1 macrophages and in a 293T cell line stably reconstituted with components of the pyrin inflammasome. Knockdown of pyrin and selective inhibition of p38 MAPK greatly attenuated caspase-1 activation by ribotoxic stress, whereas expression of the conditional mutant ΔMEKK3:ER* allowed the activation of caspase-1 without ribotoxic stress. Disruption of microtubules by colchicine also inhibited pyrin inflammasome activation by ribotoxic stress. Together, our results indicate that ribotoxic stress activates the human pyrin inflammasome through a mechanism that requires p38 MAPK signaling and microtubule stability.</P>
Mitochondria and the NLRP3 inflammasome: physiological and pathological relevance
Je-Wook Yu,Myung-Shik Lee 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.11
The NLRP3 inflammasome is assembled andactivated in certain types of myeloid cells upon sensingmicrobe-derived toxins or host-derived danger signals. Activation of the NLRP3 inflammasome by endogenousligands has been discovered in various disorders, includingmetabolic syndrome, type 2 diabetes, atherosclerosis, gout,reperfusion injury of the heart, neurodegeneration, such asAlzheimer’s disease, chronic kidney diseases, and maculardegeneration of the eyes. Despite the potential significanceof the NLRP3 inflammasome in the pathogenesis of severaldiseases, details on the activation mechanism of theNLRP3 inflammasome by a variety of stimulators have yetto be reported. Emerging evidence suggests that mito-chondrial events are associated with NLRP3 activation indisease conditions. Mitochondrial dysfunction actsupstream of NLRP3 activation by providing reactive oxy-gen species (ROS) to trigger NLRP3 oligomerization or byinducing a-tubulin acetylation to relocate mitochondria tothe proximity of NLRP3. In addition, mitochondria work asa platform for inflammasome assembly. Mitochondrialevents may also lie downstream of NLRP3 activation. While the molecular mechanisms of mitochondrial dys-function associated with NLRP3 activation are still unclear,they may involve the perturbation of mitochondria by K?efflux and subsequent intracellular disequilibrium. Thus, mitochondria and NLRP3 machinery appear to be closelyinterwoven at multiple levels.
Heat transport study of the spin liquid candidate 1T−TaS2
Yu, Y. J.,Xu, Y.,He, L. P.,Kratochvilova, M.,Huang, Y. Y.,Ni, J. M.,Wang, Lihai,Cheong, Sang-Wook,Park, Je-Geun,Li, S. Y. American Physical Society 2017 Physical Review B Vol.96 No.8
<P>We present ultralow-temperature thermal conductivity measurements on single crystals of the prototypical charge-density-wave material 1T-TaS2, which was recently argued to be a candidate for a quantum spin liquid. Our experiments show that the residual linear term of thermal conductivity at zero field is essentially zero, within experimental accuracy. Furthermore, the thermal conductivity is found to be insensitive to the magnetic field up to 9 T. These results clearly demonstrate the absence of itinerant magnetic excitations with fermionic statistics in bulk 1T-TaS2, and thus put a strong constraint on the theories of the ground state of this material.</P>
Physicochemical Property of Polygonum multiflorum by Acetic Acid Bacteria Fermentation
Kyung-Je Kim,Seong-Woo Jin,Hae-Shin Je,Young-Woo Koh,Seung-Bin Im,Sang-Wook Jeong,Yu-Seon Kim,Junseok Oh,Jae-Heoi Hong,Tae-Young Park,Kyoungsun Seo 한국버섯학회 2017 버섯 Vol.21 No.2
Polygonum multiflorum (Polygonaceae family) is effective to cholesterol lowering effect, increased immunity effect and whitening effect. P. multiflorum root is used for medicinal herb that can be used as raw material for food. In this study, acetic acid fermentation was adding extracts of P. multiflorum root(0%, 1%, 3%, 5%) for the developing healthy beverage. In this study, we investigated the contents of free sugars, organic acids and inorganic components of P. multiflorum root. As a result of free sugars from P. multiflorum root analysis, three kind of free sugars were determined the glucose, sucrose and lactose by HPLC. Four kind of organic acids were found in lactic acid fermented P. multiflorum root. And oxalic acid, lactic acid and succinic acid were detected in organic acids. The content of lactose and lactic acid in lactic acid fermented P. multiflorum root was the highest among the free sugars and organic acids. The content of minerals were in high orders of sodium> calcium> magnesium in P. multiflorum by acetic acid fermentation. The content of inorganic components was highest in lactic acid fermented solution with 5% and proportional to the content of P. multiflorum