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.

Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes

Kim, Se-Jin,Ho Hur, Joon,Park, Channy,Kim, Hyung-Jin,Oh, Gi-Su,Lee, Joon No,Yoo, Su-Jin,Choe, Seong-Kyu,So, Hong-Seob,Lim, David J,Moon, Sung K,Park, Raekil Nature Publishing Group 2015 Experimental and molecular medicine Vol.47 No.2

<P>Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine <I>in vivo</I>. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.</P>

P3 Promoter of Bovine Papillomavirus Type - 1

Choe, Joon Ho,Peter Vaillancourt,Michael Botchan 한국유전학회 1988 Genes & Genomics Vol.10 No.4

In attempt to map the structure of transcripts which contain coding sequence from the E1 and E8 ORFs of BPV-1, we have identified a new promoter which is internal to the E1 ORF. S1 nuclease protection and primer extension analysis of poly(A) cytoplasmic RNA from ID 13 cells reveal the presence of a pair of 5′ ends at nucleotides 886 and 896 which correlate well with the 5′ ends of a class of cDNA clones. In order to determine whether these 5′ ends corresponded to a functional promotor, the BPV-1 Pst I fragment from 576-1299 was tested in an in vitro transcription assay using HeLa cell extract. Primer extension analysis of the in vitro transcription products showed the presence of two cap sites which were the same as those observed for in vivo mRNA, and whose transcription was α-amanitin sensitive. Using a set of overiapping, uniformly labelled SP6 probes from nucleotides 576-1299 we showed by RNase protection analysis that the vast majority of transcripts which initiate from this promotor use the splice donor at nucleotide 1235 previously mapped. This confirms that the most abundant class of P3 cDNAs uses this leader exon. These transcripts are moderately abundant relative to the bulk of the BPV-1 mRNAs: the P3 leader exon-containing transcripts are estimated to be about 5-fold less abundant than the set of E6, E7 and E6/E7 transcripts which contain exons which use the splice donor at nucleotide 865. Analogous promotors and leader exons located in the 5′ region of the E1 ORF have been identified in HPV-6 and HPV-11.

Bayesian analysis for the bivariate Poisson regression model: Applications to road safety countermeasures

Choe, Hyeong-Gu,Lim, Joon-Beom,Won, Yong-Ho,Lee, Soo-Beom,Kim, Seong-W. The Korean Data and Information Science Society 2012 한국데이터정보과학회지 Vol.23 No.4

We consider a bivariate Poisson regression model to analyze discrete count data when two dependent variables are present. We estimate the regression coefficients as sociated with several safety countermeasures. We use Markov chain and Monte Carlo techniques to execute some computations. A simulation and real data analysis are performed to demonstrate model fitting performances of the proposed model.

The Adsorptions and Configurations of CO Molecules on W (110) and W (100) Surface: Molecular Orbital Theory

Choe, Sang-Joon,Kang, Hae-Jin,Park, Dong-Ho,Huh, Do-Sung,Lee, Soon-Bo Korean Chemical Society 2004 Bulletin of the Korean Chemical Society Vol.25 No.9

The adsorption and configuration of CO molecules adsorbed on W (110) and W (100) surfaces have been calculated by the atomic superposition and electron delocalization molecular orbital (ASED-MO) method. Referred to as the ASED-MO method, it has been used in the present study to calculate the geometries, binding energies, vibrational frequencies, orbital energies, reduced overlap population (ROP), and charges. From these results adsorption properties of ${\alpha}$-state and ${\beta}$-state were deduced. The calculated binding energies are in good agreement with the experimental result. On the W (110), the calculated average binding energies are 2.56 eV for the end-on configuration and 3.20 eV for the lying-down configuration. Calculated vibrational frequency is 1927 $cm^{-1}$ at a 1-fold site and 1161 $cm^{-1}$ at a long-bridge (2) site. These results are in reasonable agreement with experimental values. On the W(100) surface, calculated average binding energies of the end-on and the lying-down are 2.54 eV and 4.02 eV respectively. The differences for binding energy and configuration on the surfaces are explained on the basis of surface-atom coordination and atom-atom spacing. In the favored lyingdown CO configuration on the W(110) and W(100) surfaces, 4 ${\sigma}$ and 1 ${\pi}$ donation interactions, coupled with the familiar 5 ${\sigma}$ donation to the surfaces and back-donations to the CO 2 ${\pi}^{\ast}$ orbital, are responsible for adsorption to the surface.

Prevalence of painful bladder syndrome/interstitial cystitis-like symptoms in women: a population-based study in Korea

Choe, Jin Ho,Son, Hwancheol,Song, Yun Seob,Kim, Joon Chul,Lee, Jeong Zoo,Lee, Kyu-Sung Springer-Verlag 2011 World journal of urology Vol.29 No.1

A Study on Acupuncture-generated Blood- Oxygen-Level Dependant Signals in Substantia Nigra and Other Areas in Extrapyramidal Tract

Choe Il-hwan,Park Hi-joon,Yoon Hyo-woon,Shin Hyung-chul,Lee Sang-hoon,Lee Yun-ho,Lim Sabina 대한침구의학회 2008 대한침구의학회지 Vol.25 No.1

목적 : 전통적으로 태충(LR3)과 양릉천(GB34)은 운동기능과 관련된 질환에 사용되어 왔다. 우리는 두뇌에 신경독을 주입하여 파킨슨병 쥐모델을 제작하였고, 쥐는 운동기능이 손상되고 도파민성 신경세포가 선택적으로 소멸하였다. 병증 모델 쥐에게 태충과 양릉천에 자침한 결과 운동기능이 개선되고 신경세포보호효과가 나타남을 관찰한 바 있다. 이에 실제로 태충과 양릉천에 자침하여 운동기능과 관련된 추체외로 영역에서 신경의 활성화가 나타나는지를 fMRI를 통하여 관찰하였다. 방법 : 자침은 수기침을 선택하였으며, 혈위는 ① 태충, ② 양릉천, ③ 태충+양릉천의 세군데를 설정하였고, 자침에 대한 대조자극으로 피부자극을 채택하였다. fMRI 스캐너는 3T를 사용하였고 뇌신경 활성화의 신호는 BOLD(blood-oxygen-level dependant)를 관찰하였다. 두뇌에서 관찰부위는 중뇌를 중심으로 추체외로로 한정하였다. 결과 : 태충에 자침하였을 때 두뇌의 substantia nigra, subthalamic nucleus, red nucleus, pons 등이 활성화 되었다. 양릉천에 자침하였을 때 substantia nigra, subthalamic nucleus, caudate nucleus, thalamus가 활성화 되었다. 태충과 양릉천에 동시에 자침하였을 때는 substantia nigra, subthalamic nucleus, red nucleus, globus pallidus가 활성화되었다. 대조자극에 의해서는 위의 영역들이 활성화되지 않았다. 결론 : 태충, 양릉천, 태충+양릉천 자극은 대뇌에서 추체외로 영역을 활성화시키며 특히 substantia nigra의 활성화는 파킨슨병과 같은 질환의 조절가능성을 시사한다.

Adsorbed Carbon Formation and Carbon Hydrogenation for CO₂ Methanation on the Ni(111) Surface: ASED-MO Study

Choe, Sang-Joon,Kang, Hae-Jin,Kim, Su-Jin,Park, Sung-Bae,Park, Dong-Ho,Huh, Do-Sung Korean Chemical Society 2005 Bulletin of the Korean Chemical Society Vol.26 No.11

Using the ASED-MO (Atom Superposition and Electron Delocalization-Molecular Orbital) theory, we investigated carbon formation and carbon hydrogenation for $CO_2$ methanation on the Ni (111) surface. For carbon formation mechanism, we calculated the following activation energies, 1.27 eV for $CO_2$ dissociation, 2.97 eV for the CO, 1.93 eV for 2CO dissociation, respectively. For carbon methanation mechanism, we also calculated the following activation energies, 0.72 eV for methylidyne, 0.52 eV for methylene and 0.50 eV for methane, respectively. We found that the calculated activation energy of CO dissociation is higher than that of 2CO dissociation on the clean surface and base on these results that the CO dissociation step are the ratedetermining of the process. The C-H bond lengths of $CH_4$ the intermediate complex are 1.21 $\AA$, 1.31 $\AA$ for the C${\cdot}{\cdot}{\cdot}H_{(1)}$, and 2.82 $\AA$ for the height, with angles of 105${^{\circ}}$ for ∠ $H_{(1)}$CH and 98${^{\circ}}$ for $H_{(1)} CH _{(1)}$.

Anthocyanins in the black soybean (Glycine max L.) protect U2OS cells from apoptosis by inducing autophagy via the activation of adenosyl monophosphate-dependent protein kinase

CHOE, YUN-JEONG,HA, TAE JOUNG,KO, KYOUNG-WON,LEE, SUN-YOUNG,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2012 ONCOLOGY REPORTS Vol.28 No.6

<P>Anthocyanins (ATCs) have been reported to induce apoptosis in various types of cancer cells, stimulating the development of ATCs as a cancer chemotherapeutic or chemopreventive agent. It was recently reported that ATCs can induce autophagy, however, the mechanism for this remains unclear. In the present report, we carried out mechanistic studies of the mechanism involved in ATC-induced autophagy using ATCs extracted from black soybeans (cv. Cheongja 3, Glycine?max?L.). ATCs clearly induced hallmarks of autophagy, including LC3 puncta formation and the conversion of LC3-I to LC3-II in U2OS human osteosarcoma cells. The induction of autophagy was accompanied by the phosphorylation of multiple protein kinases including extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), protein kinase B (AKT) and adenosyl mono-phosphate-dependent protein kinase (AMPK). While chemical inhibitors against ERK1/2, p38 MAPK, JNK and AKT failed to inhibit ATC-induced autophagy, the suppression of AMPK by compound C (CC) as well as siRNA against AMPK reduced ATC-induced autophagy. The treatment of ATCs resulted in a decrease in intracellular ATP contents and the activation of AMPK by AICAR treatment also induced autophagy. It is noteworthy that the reduction of autophagy via the inhibition of AMPK resulted in enhanced apoptosis in ATC-treated cells. In addition, siRNA against forkhead box O3A (FOXO3a), a downstream target of AMPK, suppressed ATC-induced autophagy and p27KIP1 siRNA increased apoptosis in ATC-treated cells. Collectively, it can be concluded that ATCs induce autophagy in U2OS cells via activation of the AMPK-FOXO3a pathway and protect cells from ATC-induced apoptosis via the AMPK-p27KIP1 pathway. These results also suggest that autophagy-modulating agents could contribute to the efficient development of ATCs as anticancer therapy.</P>

Low Voltage Program/Erase Characteristics of Si Nanocrystal Memory with Damascene Gate FinFET on Bulk Si Wafer

Choe, Jeong-Dong,Yeo, Kyoung-Hwan,Ahn, Young-Joon,Lee, Jong-Jin,Lee, Se-Hoon,Choi, Byung-Yong,Sung, Suk-Kang,Cho, Eun-Suk,Lee, Choong-Ho,Kim, Dong-Won,Chung, Il-Sub,Park, Dong-Gun,Ryu, Byung-Il The Institute of Electronics and Information Engin 2006 Journal of semiconductor technology and science Vol.6 No.2

We propose a damascene gate FinFET with Si nanocrystals implemented on bulk silicon wafer for low voltage flash memory device. The use of optimized SRON (Silicon-Rich Oxynitride) process allows a high degree of control of the Si excess in the oxide. The FinFET with Si nanocrystals shows high program/erase (P/E) speed, large $V_{TH}$ shifts over 2.5V at 12V/$10{\mu}s$ for program and -12V/1ms for erase, good retention time, and acceptable endurance characteristics. Si nanocrystal memory with damascene gate FinFET is a solution of gate stack and voltage scaling for future generations of flash memory device. Index Terms-FinFET, Si-nanocrystal, SRON(Si-Rich Oxynitride), flash memory device.