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Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53
CHOE, YUN-JEONG,LEE, SUN-YOUNG,KO, KYUNG WON,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2014 International journal of oncology Vol.44 No.3
A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-alpha, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin-3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-beta, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-beta reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.
Plyometric Training과 비타민 C 투여가 남고생의 체력, 혈중 젖산, 암모니아 및 젖산탈수소효소에 미치는 영향
장준원,김세종,이현미,서혜림,조현숙,고정림,염종우,예정복,백영호 釜山大學校 附設 體育科學硏究所 2003 體育科學硏究所 論文集 Vol.19 No.-
The purpose of this was to examine the effect of plyometric training and vitamin C ingestion on physical fitness and fatigue substance....
윤정수,고윤영,이호준 제주대학교 해양과환경연구소 2001 해양과환경연구소 연구논문집 Vol.25 No.-
Thirteen surface sediment samples collected from the central area of the Yellow Sea, were analyzed for their contents of thirteen metallic elements, including Al, Fe, Ca, Mg, K, Na, Cu, Cr, Ni, Pb, Co, Zn and Mn, as well as their grain-size and organic carbon content. The sandy sediment facies are distributed in the eastern area, the sandy mud and clay sedimentary facies are distributed in the central region, and a patch of fine-grained mud is exists in the western central part. The content of organic carbon which ranges from 0.3 to 1.3% in the sediment showed increase with the decrease of grain-size, and that is dominantly high concentration in the western mud patch region. The total concentration of A1, Fe, Ca, and Mn are higher in the northwestern part near toward the Shandong Peninsula and its decreased the eastern and southeastern part far away from the Huanghe River. This distribution patterns are well coincide with grain-size. The elements content such as Cu, Ni, and Cr are enriches in the southwestern mud patch region and it seems to be partly influence by the Changjiang Diluted Plume.
( Joon Ho Ko ),( Tae Hyoung Gim ),( Se Hee Lee ),( Jin Seop Shim ) 서울시정개발연구원 2011 연구보고서 Vol.2011 No.1
As the Seoul Metropolitan Government (SMG) is trying to encourage the use of electric vehicles as the Green Car Smart City declaration, it is necessary to develop an electric vehicle (EV) delivery plan considering Seoul`s transportation characteristics. This study aims to identify strategies and issues associated with the introduction of various types of EVs based on transportation data. In addition, this study proposes organizational frameworks for fulfilling the plan and estimates benefits such as emissions reduction and energy savings and costs for the plan implementation. Although the SMG set up a plan for delivering more than 20,000 private EVs among the total 40,000 EVs, the encouragement of the private EV use was found to be significantly difficult because of high EV prices and short of charging infrastructure. Meanwhile, taxies and buses were found to be less difficult and more economical because of their long travel distances, fixed route operations (for buses) and easier installment of charging stations in depot. For EV taxies, pilot projects may be implemented cooperating with large taxi companies with more than 100 fleet. The location of rapid charging stations may be detemiined depending on the amount of taxi traffic volumes. In the case of EV buses, buses operated on rather short routes, for example less than 20km can be the target. In addition, some portions of motorcycles and rental cars may be converted to EVs. For private EVs, 3,500 EVs may be on the road by mid 2013, which include 2,200 new cars annually, 720 company fleet vehicles, 150 rental cars and 390 car sharing fleet. Concerning rapid charging facilities, 80 charging posts located at 40 different places may be provided in order to ease the EV drivers` anxiety. Candidate locations would be district offices, near the ramps of inner circular expressway, roadways crossing the city boundary and Hangang bridges. Besides these, 20 more fast charging posts may be installed in 10 depots of company taxies. For public standard chargers, several public facilities such as public parking lots, civic centers and libraries would be candidate locations. In the private sector, large buildings with a floor area of more than 30,000m2 would be the target for the installment of chargers. The pace of the charging facility provision should be coupled with the number of EV purchases. The proposed ratio of the numbers of EVs to public chargers are 5:1 until mid 2013, and after then the ratio may be adjusted to 8:1. These plans would be implemented by public-private partnership where the SMG may provide administrative and financial supports. As an active measure, the SMG may take the role to lead the plans, directly managing and controlling the EVs by setting up an EV center. The analysis on expected benefits and costs for the deployment of 40,000 EVs indicated that Seoul may see greater benefits of emissions reduction and fuel savings than the cost incurred by EV purchase subsidy and infrastructure construction. In more detail, the analyses suggested that B/C ratio for the four vehicle types (private car, bus, taxi, and motorcycle) would range between 0.90 and 1.01 depending on electricity prices if the benefits last five years. If it lasts seven years, B/C ratio would range between 1.26 and 1.41. Considering that the B/C ratio of private EV sector resulted in only 0.49~0.77, the public sector EVs such as taxies and buses would generate great benefits. Meanwhile, the low B/C ratio for the private EVs implies that government should lead the promotion of EV uses in the private sector for vitalizing related industries and spreading environment friendly transportation modes.