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      • KCI등재

        PGA2-induced expression of HO-1 is mediated by transcriptional upregulation of Nrf2

        Sang-sun Lee,Yun-Jeong Choe,Hyein Lee,Sun-Young Lee,Ho-Shik Kim 대한독성 유전단백체 학회 2019 Molecular & cellular toxicology Vol.15 No.2

        Backgrounds: Prostaglandin (PG) A2 reportedly stimulated expression of heme oxygenase (HO)-1 at the level of transcription via the activation of p38MAPK. Details of the mechanism, however, have not been provided, and this includes identification of the transcription factors responsible for PGA2-induced HO-1 expression. Herein is described an analysis of the role of nuclear factor erythroid 2 related factor 2 (Nrf2) and how PGA2 increases the activity of Nrf2 during PGA2-induced HO-1 expression. Methods: Expressions of HO-1 and Nrf2 were analyzed at the levels of both mRNA and protein. Nrf2 siRNA, SB203580, an inhibitor of p38MAPK, and scavengers of reactive oxygen species (ROS) were used to identify the effects of Nrf2, p38MAPK and ROS on PGA2-induced HO-1 expression. Results: Although SB203580 suppressed PGA2-induced HO-1 expression, genetic activation of p38MAPK could not stimulate the transcription of HO-1. Cycloheximide (CHX), an inhibitor of protein translation, almost completely prevented PGA2-induced increase of HO-1 transcription, but it did not prevent the phosphorylation of p38MAPK, which suggests that both de novo protein synthesis and p38MAPK activity are required to induce the transcription of HO-1 in response to PGA2 treatment. In addition, PGA2 increased the level of both Nrf2 mRNA and protein in a dose-dependent manner. Knockdown of Nrf2 using small interfering RNA (siRNA) suppressed PGA2-induced HO-1 expression. The PGA2-induced transcription of Nrf2 was prevented by ROS scavengers such as n-acetyl-l-cysteine and tempol but not CHX. Furthermore, siRNA against p38MAPK did not change the level of nuclear Nrf2 protein. Conclusion: These findings suggest that PGA2 induces HO-1 transcription via an increase in Nrf2 protein, the transcription of which is initiated by an accumulation of ROS that is independent of the p38MAPK activation pathway.

      • KCI등재

        PGA2 induces the expression of HO-1 by activating p53 in HCT116 cells

        Hyein Lee,Sang-Sun Lee,Ji-Young Park,Yun-Jeong Choe,이선영,Ho-Shik Kim,H.-S. Kim 대한독성 유전단백체 학회 2017 Molecular & cellular toxicology Vol.13 No.2

        Prostaglandin (PG) A2 which is a cytotoxic PG, was reported to induce the expression of heme oxygenase (HO)-1 via activation of p38MAPK to keep U2OS cells from cell cycle arrest in G2M phase. The expression of HO-1 is primarily regulated at the level of transcription. But the transcription factors that are responsible for PGA2-induced HO-1 expression were not clarified yet. Here, we report that PGA2-induced transcription of HO-1 is mediated by p53, a tumor suppressive transcription factor. In HCT116 cells, PGA2 treatment led to the phosphorylation of p53 and an increase of p21WAF1 transcription as well as the activation of HO-1 transcription. Knocking p53 down via RNA interference or inhibiting the p53’s transcriptional activity by pifithrin-α treatment led to suppression of the increase in the level of both HO-1 expression and activity of HO-1 promoter. Pretreatment of NU- 7441, a chemical inhibitor of DNA-activated protein kinase (DNA-PK), prevented both the PGA2-induced phosphorylation of p53 and an increase of HO-1 transcription. In addition, N-acetyl-l-cysteine, a scavenger of reactive oxygen species (ROS), also mimicked the effect of NU-7441 on the PGA2-induced activation of p53 and HO-1 transcription. Collectively, these results suggest that PGA2 induces the expression of HO-1 via activation of p53, which is mediated by the ROSDNA- PK pathway.

      • KCI등재
      • SCOPUSKCI등재

        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>

      • KCI등재

        Comparison of the Diagnostic Ability of Endoscopic Ultrasonography and Abdominopelvic Computed Tomography in the Diagnosis of Gastric Subepithelial Tumors

        Sang Yoon Kim,Ki-Nam Shim,Joo-Ho Lee,Ji Young Lim,Tae Oh Kim,A. Reum Choe,Chung Hyun Tae,Hye-Kyung Jung,Chang Mo Moon,Seong-Eun Kim,Sung-Ae Jung 대한소화기내시경학회 2019 Clinical Endoscopy Vol.52 No.6

        Background/Aims: Endoscopic ultrasonography (EUS) is the most effcient imaging modality for gastric subepithelial tumors (SETs). However, abdominopelvic computed tomography (APCT) has other advantages in evaluating the characteristics, local extension,or invasion of SETs to adjacent organs. This study aimed to compare the diagnostic ability of EUS and APCT based on surgicalhistopathology results. Methods: We retrospectively reviewed data from 53 patients who underwent both EUS and APCT before laparoscopic wedge resectionfor gastric SETs from January 2010 to December 2017 at a single institution. On the basis of histopathology results, we assessed thediagnostic ability of the 2 tests. Results: The overall accuracy of EUS and APCT was 64.2% and 50.9%, respectively. In particular, the accuracy of EUS vs. APCT for thediagnosis of gastrointestinal stromal tumors (GISTs), leiomyomas, and ectopic pancreas was 83.9% vs. 74.2%, 37.5% vs. 0.0%, and 57.1%vs. 14.3%, respectively. Most of the incorrect diagnoses with EUS involved hypoechoic lesions originating in the fourth echolayer, withthe most common misdiagnosed lesions being GISTs mistaken for leiomyomas and vice versa. Conclusions: APCT showed a lower overall accuracy than EUS; however, APCT remains a useful modality for malignant/potentiallymalignant gastric SETs.

      • Cutaneous atypical mycobacterial infection by Mycobacterium intracellulare detected by Pcr-reverse blot hybridization assay

        ( Sung Jay Choe ),( Hee Chul Chung ),( Eung Ho Choi ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.1

        A 41-year-old male visited to the dermatologic department due to multiple erythematous to violaceous welldemarcated papules and nodules on neck and upper chest of 4 months’ duration, which were not respond to several antibiotics and antifungals. He has no compromised immune status. A biopsy of the lesion revealed poorly formed granulomatous infiltration of lymphocytes with multinucleated giant cells. Nested PCR for mycobacterium tuberculosis and non-tuberculous mycobacterium (NTM) were negative. However, because atypical mycobacterial infection was highly suspected both clinically and histologically, we additionally performed reverse blot hybridization assay (REBA) for mycobacterium. Through REBA, Mycobacterium intracellulare infection was diagnosed, and the patient was started treatments. After 3 months, most of the cutaneous lesions were improved. The gold standard for a definite diagnosis of NTM is to detect Mycobateria on culture; however, this method is time-consuming, resulting in a delayed diagnosis. Nested PCR is currently widely used to diagnosis Mycobacterium infection. REBA is a method of hybridizing the PCR products of DNA extracted from Mycobacterium-infected specimens on a prepared DNA template of Mycobacteria. This is a case of cutaneous atypical mycobacterial infection by Mycobacterium intracellulare, confirmed by REBA followed by the corresponding treatment.

      • SCISCIESCOPUS

        The mRNP remodeling mediated by UPF1 promotes rapid degradation of replication-dependent histone mRNA

        Choe, Junho,Ahn, Sang Ho,Kim, Yoon Ki Oxford University Press 2014 Nucleic acids research Vol.42 No.14

        <P>Histone biogenesis is tightly controlled at multiple steps to maintain the balance between the amounts of DNA and histone protein during the cell cycle. In particular, translation and degradation of replication-dependent histone mRNAs are coordinately regulated. However, the underlying molecular mechanisms remain elusive. Here, we investigate remodeling of stem-loop binding protein (SLBP)-containing histone mRNPs occurring during the switch from the actively translating mode to the degradation mode. The interaction between a CBP80/20-dependent translation initiation factor (CTIF) and SLBP, which is important for efficient histone mRNA translation, is disrupted upon the inhibition of DNA replication or at the end of S phase. This disruption is mediated by competition between CTIF and UPF1 for SLBP binding. Further characterizations reveal hyperphosphorylation of UPF1 by activated ATR and DNA-dependent protein kinase upon the inhibition of DNA replication interacts with SLBP more strongly, promoting the release of CTIF and eIF3 from SLBP-containing histone mRNP. In addition, hyperphosphorylated UPF1 recruits PNRC2 and SMG5, triggering decapping followed by 5′-to-3′ degradation of histone mRNAs. The collective observations suggest that both inhibition of translation and recruitment of mRNA degradation machinery during histone mRNA degradation are tightly coupled and coordinately regulated by UPF1 phosphorylation.</P>

      • Efficacy and safety of guselkumab compared with placebo and adalimumab in Korean patients with moderate to severe psoriasis: Post-hoc analysis from the phase Ⅲ, double-blind, placebo- and active comparator-controlled VOYAGE1/2 trials

        ( Sang Woong Youn ),( Tae Yoon Kim ),( Byung Soo Kim ),( Seung Chul Lee ),( Jeung Hoon Lee ),( Yong-beom Choe ),( Joo-heung Lee ),( Jee-ho Choi ),( Joo Young Roh ),( Seong Jin Jo ),( Eun-so Lee ),( Mi 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

        Background: The Phase Ⅲ studies, VOYAGE 1 and 2, were conducted to assess guselkumab for the treatment of patients with moderate to severe psoriasis. However, these studies included a worldwide study population. Objectives: To determine the efficacy and safety of guselkumab in Korean patients. Methods: This analysis included 28 patients from VOYAGE 1 and 98 patients from VOYAGE 2. In total, 126 patients were analyzed. Outcomes through week 28 were analyzed due to differences in design after week28. Results: Of 126 Korean patients randomized, 30 received placebo, 63 were assigned to guselkumab, and 33 received adalimumab. Guselkumab was superior to adalimumab in achieving an IGA 0 score (clear skin) at week 12 (31.7% vs 0.0%, p<0.001) and at week 24 (52.4% vs 21.2%, p=0.004), respectively. Among patients treated with guselkumab, 40 of 63 (63.5%) achieved a PASI75 response at week 8; at week 24, a significantly higher proportion of guselkumab patients achieved a PASI 75 compared to adalimumab patients (93.7% vs 66.7%, respectively, p<0.001). In addition, higher proportions of guselkumab patients achieved PASI 90 and PASI 100 than adalimumab patients at week 24 (PASI90; 73.0% vs 57.6%, p=0.168 / PASI100; 20.6% vs 15.2%, p=0.591, respectively). Through week 28, guselkumab and adalimumab showed comparable safety profiles. Conclusion: The efficacy and safety of guselkumab in Korean psoriasis patients through 28 weeks was consistent with findings reported for the VOYAGE1 and 2 trials.

      • SCIESCOPUSKCI등재

        Effects of Ripening Conditions on the "Lomo embuchado" Sausage Quality

        Ho Sung Choe,Kwan Seob Shim,Jong Hyun Jung,Yi Hyung Chung,Dae Keun Shin 한국축산식품학회 2014 한국축산식품학회지 Vol.34 No.3

        The objective of this study was to investigate the effects of two different ripening durations, with, or without adding rosemary powder, on Lomo embuchado (LEO) sausage quality. All LEOs were ripened for two different durations, 45 or 60 d, with, or without the addition of rosemary powder, as follows: 1) LEO ripened for 45 d (LER45), 2) LEO ripened for 60 d (LER60), 3) rosemary LEO ripened for 45 d (RLE45), and 4) rosemary LEO ripened for 60 d (RLE60). Significant differences were observed in both moisture and ash content, with higher moisture and less ash content in LER45 (p<0.05). No trend was shown in the crude protein content of the four different treatments, but significantly low protein content was shown only in RLE45 (p<0.05). Ripening for 45 d improved the lightness, yellowness, and water activity of LEOs (p<0.05). However, ripening duration together with rosemary powder addition had no significant effects on redness (p>0.05). The LER45 generated significantly improved chewiness, gumminess, and hardness, as compared to both LER60 and RLE60 (p<0.05). In conclusion, the results suggest that ripening for 45 d seems to enhance LEO quality, but that rosemary powder addition may not be required to develop good LEO quality.

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