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Novel signaling axis for ROS generation during K-Ras-induced cellular transformation
Park, M-T,Kim, M-J,Suh, Y,Kim, R-K,Kim, H,Lim, E-J,Yoo, K-C,Lee, G-H,Kim, Y-H,Hwang, S-G,Yi, J-M,Lee, S-J Macmillan Publishers Limited 2014 CELL DEATH AND DIFFERENTIATION Vol.21 No.8
Reactive oxygen species (ROS) are well known to be involved in oncogene-mediated cellular transformation. However, the regulatory mechanisms underlying ROS generation in oncogene-transformed cells are unclear. In the present study, we found that oncogenic K-Ras induces ROS generation through activation of NADPH oxidase 1 (NOX1), which is a critical regulator for the K-Ras-induced cellular transformation. NOX1 was activated by K-Ras-dependent translocation of p47<SUP>phox</SUP>, a subunit of NOX1 to plasma membrane. Of note, PKCδ, when it was activated by PDPK1, directly bound to the SH3-N domain of p47<SUP>phox</SUP> and catalyzed the phosphorylation on Ser348 and Ser473 residues of p47<SUP>phox</SUP> C-terminal in a K-Ras-dependent manner, finally leading to its membrane translocation. Notably, oncogenic K-Ras activated all MAPKs (JNK, ERK and p38); however, only p38 was involved in p47<SUP>phox</SUP>-NOX1-dependent ROS generation and consequent transformation. Importantly, K-Ras-induced activation of p38 led to an activation of PDPK1, which then signals through PKCδ, p47<SUP>phox</SUP> and NOX1. In agreement with the mechanism, inhibition of p38, PDPK1, PKCδ, p47<SUP>phox</SUP> or NOX1 effectively blocked K-Ras-induced ROS generation, anchorage-independent colony formation and tumor formation. Taken together, our findings demonstrated that oncogenic K-Ras activates the signaling cascade p38/PDPK1/PKCδ/p47<SUP>phox</SUP>/NOX1 for ROS generation and consequent malignant cellular transformation.
Relationship between Stress Gene Polymorphisms and Litter Size by AI in Pigs
Jin, H.J.,Kim, I.C.,Wee, M.S.,Yeon, S.H.,Kim, C.D.,Lee, S.S.,Cho, C.Y.,Cho, S.R.,Son, D.S.,Park, C.K. 韓國受精卵移植學會 2007 한국동물생명공학회지 Vol.22 No.4
This study was performed to investigate the relationship between PSS-HSP70 gene polymorphism and artificial insemination (AI) reproductivity in the pigs. The RFLP polymorphism of PSS and the SSCP polymorphisms of HSP70 K1, K3 and K4 PCR product were detected different patterns. In the experiment for AI of fresh semen, spring and fall season showed higher litter size born of 10.89 head than 10.47 head of summer season. Landrace was showed higher litter size of 9.96 head than that of Duroc and Yorkshire (p<0.05). Stress relating PSS and HSP70 polymorphism of PSS-Normal, HSP70 K1-BB, K3-AB, K4-AA showd a highest litter size born of 10.97 head and litter size born alive of 10.69 head than that of the other polymorphisms(p<0.05). In the experiment for AI of frozen semen, effects of season and pig breeds were not showed for litter size born. The stress relating polymorphism of PSS-Carrier, HSP70 K1-BB, K3-BB, K4-AB showed highest litter size born of 11.29 head and litter size born alive of 10.82 head and PSS-Normal, HSP70 K1-BB, K3-AB, K4-AA showed the lowest litter size born of 8.48 head and litter size born alive of 7.33 head than that of the other polymorphisms(p<0.05). These results suggest that AI litter size born for the stress of forzen thawed semen may be affected by PSS and HSP70 polymorphism in pigs.
김미란,기선호,배현주,장우현,박선양,최강원 대한감염학회 1995 감염 Vol.27 No.4
목적:쯔쯔가무시질환시 생기는 전신혈액응고장애의 병인 기전이 rickettsia의 침투에 의한 혈관내피세포의 손상, 그에 따른 tissue factor의 발현, 뒤이은 tissue type plasminogen activator(tPA)의 분비와 보상기전으로 type 1 plasminogen activator inhibitor(PAI-1)이 분비되는 과정으로 생각하고 이를 보고자 연구를 시행하였다. 방법:체외배양한 혈관내피세포에 순수분리한 Rickettsia tsutsugamushi를 감염시킨후 상층액에서 ELISA법으로 tPA와 PAI-1을 측정하였고 혈관내피세포 단층배양에서 면역형광법으로 tissue factor를 측정하였으며 PAI-1 유전자의 발현을 확인하고자 Northern blot analysis로 PAI-1 mRNA를 확인하였다. 결과: 1) PAI-1 R. tsutsugamushi를 감염시킨후 24시간에 가장 높은 농도를 보이며 그 증가량은 정상대조군에 비해 2.5배에서 4.7배까지 증가 하였다. 2) R. tsutsugamushi를 감염시킨후 혈관내피세포에서 분비되는 tPA의 분비는 정상대조군에 비해 유의한 차이를 보이지 않았다. 3) Northern blot analysis에 의한 PAI-1 mRNA의 발현 검색 결과 정상대조군에 비해 R. tsutsugamush가 감염된 혈관내피세포에서는 PAI-1의 발현이 2.5배 정도 증가하였다. 4) 혈관내피세포 단층배양에 R. tsutsugamushi를 감염시킨후 24시간에 tissue factor단일클론 항체와 FITC-conjugated anti mouse IgG를 이용한 간접 면역형광항체법으로 tissue factor를 측정한 결과 혈관내피세포 표면에서 tissue factor의 존재를 확인할 수 있었다. 결론:단층배양한 혈관내피세포에 R. tsutsugamushi를 감염시켰을 때 tissue factor가 발현되었고 PAI-1의 분비가 증가하여 24시간에 가장 많이 분비되었다. 그러나 tPA의 분비는 정상대조군에 비해 유의한 차이를 보이지 않았다. Nothern blot analysis를 통한 PAI-1 mRNA의 발현 검색 결과 PAI-1이 새로이 생성되어 분비됨을 확인하였다. Background:Tissue type plasminogen activator(tPA), type 1 plasminogen activator inhibitor (PAI-1), and von Willebrand factor are known to be released into the sera of patients in disseminated intravascular coagulation(DIC). The main pathologic mechanism of tsutsugamushi disease is the vasculitis by direct endothelial cell invasion by R. tsutsugamushi which dosen't have endotoxin. It is suspected that the mechanisms of DIC and activation of plasminogen activation system are different from those of sepsis by other organisms. which is caused by endotoxin. We suspect that direct rickettsial invasion of endothelial cells causes endothelial cell damage, tissue factor release, which is followed by DIC, and tPA and PAI-1 are released as compensatory mechanism. Methods:We cultured endothelial cells from human umbilical cord vein, infected them with purified R. tsutsugamushi Gilliam strain, checked tPA and PAI-1 by ELISA in culture supernatant. Then we observed the tissue factor expression on cultured endothelial cell monolayer by indirect IF stain. PAI-1 gene expression was evaluated by northern blot analysis. Results: 1) PAI-1 level showed gradual increase up to 240ng/ml (2.5-4.7 fold increase) in 24 hours. 2) tPA level showed no significant change with time. 3) PAI-1 gene expression increased 2.5 fold by northern blot analysis. 4) Tissue factor was expressed on the endothelial cells infected with R. tsutsugamushi. Conclusion: R. tsutsugamushi infection induces expression of tissue factor on endothelial cells and PAI-1 synthesis and it would contribute to DIC mechanism in tsutsugamushi disease in part. But it has no direct effect on tPA release.
Relationship between Stress Gene Polymorphisms and Litter Size by AI in Pigs
H. J. Jin,I. C. Kim,M. S. Wee,S. H. Yeon,C. D. Kim,S. S. Lee,C. Y. Cho,S. R. Cho,D. S. Son,C. K. Park,Z. D. Li 사단법인 한국동물생명공학회 2007 한국동물생명공학회지 Vol.22 No.4
This study was performed to investigate the relationship between PSS-HSP70 gene polymorphism and artificial insemination (AI) reproductivity in the pigs. The RFLP polymorphism of PSS and the SSCP polymorphisms of HSP70 K1, K3 and K4 PCR product were detected different patterns. In the experiment for AI of fresh semen, spring and fall season showed higher litter size born of 10.89 head than 10.47 head of summer season. Landrace was showed higher litter size of 9.96 head than that of Duroc and Yorkshire(p<0.05). Stress relating PSS and HSP70 polymorphism of PSS-Normal, HSP70 K1-BB, K3-AB, K4-AA showd a highest litter size born of 10.97 head and litter size born alive of 10.69 head than that of the other polymorphisms(p<0.05). In the experiment for AI of frozen semen, effects of season and pig breeds were not showed for litter size born. The stress relating polymorphism of PSS-Carrier, HSP70 K1-BB, K3-BB, K4-AB showed highest litter size born of 11.29 head and litter size born alive of 10.82 head and PSS-Normal, HSP70 K1-BB, K3-AB, K4-AA showed the lowest litter size born of 8.48 head and litter size born alive of 7.33 head than that of the other polymorphisms(p<0.05). These results suggest that AI litter size born for the stress of forzen thawed semen may be affected by PSS and HSP70 polymorphism in pigs.
Influence of continental outflow events on the aerosol composition at Cheju Island,South Korea
Park, John K.,Arimoto, Richard,Savoie, Dennis,Carmichael, Gregory R,Prospero, Joseph,Hong, Min-Sun,Ueda, Hiromasa,Murano, Kentaro,Chen, Li-Ling,Kim, Y. P.,Shim, Shang,Lee, Ho-geun,Song, Chul H.,Kang, 濟州大學校 基礎科學硏究所 1998 基礎科學硏究 Vol.11 No.1
The chemical composition of aerosols measured at Cheju Island, Korea, over the 3-year period March 1992 to February 1995 are presented and discussed, with a particular emphasis on the Pacific Exploratory Mission in the Western Pacific (PEM-West B) time period. Cheju Island is under the influence of continental outflow conditions nearly 70% of the year, and as a result the aerosol loading of sea salt as well as continental aerosol components is high. The 3-year mean values derived from the daily tape filters are non-sea-salt (nss) SO₄²?=6.8㎍/㎥, NO₃?=1.2㎍/㎥, Cl??=1.9㎍/㎥, Na+=1.7㎍/㎥, Ca²?=0.5㎍/㎥, NH₄?=1.3㎍/㎥, Mg²?=0.3㎍/㎥, and K+=0.4㎍/㎥. Sea-salt components show peak values in winter, while calcium, nitrate, potassium, and to a lesser extent, sulfate and ammonium, show higher values in the spring, and all species exhibit a pronounced minimum in summer. Trajectory and principal component analysis show that elevated levels of primary aerosols (both sea salt and soil-derived) occur with strong wind conditions associated with winter and spring, and high concentrations of non-sea-salt components are most strongly associated with springtime continental outflow events. During the PEM-West B period, nitrate and calcium are found to be ∼60% higher than the annual mean, sea-salt components ∼30% higher, and sulfate ∼10% higher. The aerosol data are combined with gaseous SO₂ concentrations, precipitation chemistry data and companion aerosol measurements taken at the same site, to provide further insights into the aerosol composition at Cheju. At Cheju, sulfate and ammonium are found mostly in the fine fraction (∼80 to 90%), while calcium and nitrate reside in the coarse size fraction. sulfate and nitrate are not associated with the primary aerosols, but rather become associated with the aerosol during the long-range transport process.