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.

Heme oxygenase-1 mediated protective effect of methyl gallate on cadmium-induced cytotoxicity in cultured mouse mesangial cells

Cha, Seok-Ho,Suh, Chang-Kook The Korean Society of Toxicogenomics and Toxicopro 2010 Molecular & cellular toxicology Vol.6 No.2

To clarify the effect of a phytochemical, methyl gallate (MG) on a heavy metal (cadmium)-induced renal toxicity, cytotoxicity and the change of heme oxygenase-1 (HO-1) gene expression was studied using cultured mouse renal glomerular mesangial cells (MMC). By employing RT-PCR and Western blotting analysis, we have examined the HO-1 induction in MMCs that were treated with $Cd^{2+}$ and/or MG. Using MTT assay we have also examined the cytoprotective effect of HO-1 induction against the cytotoxicity caused by toxic dose of $Cd^{2+}$. In MMCs exposed to $Cd^{2+}$ and MG, expression of HO-1 (mRNA and protein) was increased in a concentration- and time-dependent manner. The increments of HO-1 mRNA and protein expressions by $Cd^{2+}$ and MG were inhibited by the treatment of the cells with actinomycin D, an inhibitor of transcription. The decreased viability of the cells by $Cd^{2+}$ was partially recovered by the treatment of MG and this recovery by the MG was reduced by the treatment of zinc protoporphyrin IX (a HO-1 inhibitor). From these results, methyl gallate might have cytoprotective effect on $Cd^{2+}$-induced cytotoxicity that is related with heme oxygenase-1 induction.

Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7

<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</P>

Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

Sokho Kim,Myung-Hoon Oh,Bum-Seok Kim,Won-Il Kim,Ho-Seong Cho,Byoung-Yong Park,Chul Park,Gee-Wook Shin,Jungkee Kwon 고려인삼학회 2015 Journal of Ginseng Research Vol.39 No.4

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been suffi- ciently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to 200mM) for 1 h before treatment with 1 mg/ mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

Kim, Sokho,Oh, Myung-Hoon,Kim, Bum-Seok,Kim, Won-Il,Cho, Ho-Seong,Park, Byoung-Yong,Park, Chul,Shin, Gee-Wook,Kwon, Jungkee The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.4

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been sufficiently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to $200{\mu}M$) for 1 h before treatment with 1 mg/mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

사례보고 : 하수오 복용 후 발생한 재발성 독성 간염 1예

배상훈 ( Sang Hoon Bae ),김동현 ( Dong Hyun Kim ),배영석 ( Young Seok Bae ),이광재 ( Kwang Jae Lee ),김동완 ( Dong Wan Kim ),윤정빈 ( Jeoung Bin Yoon ),홍준호 ( Joon Ho Hong ),김상현 ( Sang Hyun Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2

Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.

Ln₃Ba?Co₄O? (Ln = Sm, Pr, Er, Gd, Ho) 상의 합성과 결정구조에 관한 연구

송민석,이재열,송수호 嶺南大學校 工業技術硏究所 1998 工業技術硏究所論文集 Vol.26 No.2

The Ln₃Ba?Co₄O? phases were synthesized with Pr?O? Sm₂O₃, Er₂O₃, Gd₂O₃, Ho₂O₃, BaCO₃, and Co₃O₄by solid state reaction at 1200℃ with intermittent grinding. The phases with Pr and Sm formed hexagonal structure isostructural with Nd₃Ba?Co ₄O? phase Whereas the phases with Er, Ho, and Gd formed unknown cubic phases. The crystal structure of Sm₃Ba?Co₄O? phase were refined by X-ray diffraction powder data by means of Rietveld method. The starting model was based on the Nd₃Ba?Co₄O? structure. The Crystal system was hexagonal, space group P6₃mc, a=11.634(6)A, c=6.861(4)A for pr₃Ba?Co₄O? ; a=11.556(6)A, c=6.788(3)A for Sm₃Ba?Co₄O?. Final R values are : Rwp=0.121, Rp=0.084 for pr₃Ba?Co₄O?, Rwp=0.101, Rp=0.077 for Sm₃Ba?Co₄O? .

Anti-Inflammatory Effect of By-Products from<i>Haliotis discus hannai</i>in RAW 264.7 Cells

Rho, Ho-Seok,Kim, Hyang,Kim, Jung-Ae,Karadeniz, Fatih,Ahn, Byul-Nim,Nam, Ki-Ho,Seo, Youngwan,Kong, Chang-Suk Hindawi Limited 2015 Journal of chemistry Vol.2015 No.-

<P>Several reports promoted the potential of shellfish due to their ability to act as antioxidant, anti-inflammatory, and antimicrobial agents. Pacific abalone,<I>Haliotis discus hannai</I>viscera is, reported to possess bioactivities such as antioxidative stress and anti-inflammatory. In this study, anti-inflammatory potential of mucus-secreting glands from shell-shucking waste of<I>H. discus hannai</I>was evaluated using RAW 264.7 mouse macrophage cell model. Results indicated that presence of<I>H. discus hannai</I>mucosubstance by-products (AM) significantly lowered the nitric oxide (NO) production along the expressional suppression of inflammatory mediators such as cytokines TNF-<I>α</I>, IL-1<I>β</I>, and IL-6 and enzymes iNOS and COX-2. Also, AM was shown to increase expression of anti-inflammatory response mediator HO-1. Presence of AM also scavenged the free radicals<I>in vitro</I>. In conclusion, by-products of<I>H. discus hannai</I>are suggested to possess notable anti-inflammatory potential which promotes the possibility of utilization as functional food ingredient.</P>

급성 뇌경색 환자에서 경색 위치가 심근 효소치 상승에 미치는 영향

윤경호,박현영,박성욱,장혁,김요식,조광호,유남진,김남호,오석규,정진원 圓光大學校 醫科學硏究所 2003 圓光醫科學 Vol.18 No.2

3차원 전산화단층촬영 영상을 이용한 안면 연조직 두께 계측의 임상적 유용성

정호걸,김기덕,한승호,허경석,이제범,박혁,최성호,김종관,박창서 대한구강악안면방사선학회 2006 Imaging Science in Dentistry Vol.36 No.2

Purpose : To evaluate clinical usefulness of facial soft tissue thickness measurement using 3D computed tomographic images. Materials and Methods : One cadaver that had sound facial soft tissues was chosen for the study. The cadaver was scanned with a Helical CT under following scanning protocols about slice thickness and table speed; 3 mm and 3 mm/sec, 5 mm and 5 mm/sec, 7 mm and 7 mm/sec. The acquired data were reconstructed 1.5, 2.5, 3.5 mm reconstruction interval respectively and the images were transferred to a personal computer. Using a program developed to measure facial soft tissue thickness in 3D image, the facial soft tissue thickness was measured. After the ten-time repeation of the measurement for ten times, repeated measure analysis of variance (ANOVA) was adopted to compare and analyze the measurements using the three scanning protocols. Comparison according to the areas was analyzed by Mann-Whitney test. Results : There were no statistically significant intraobserver differences in the measurements of the facial soft tissue thickness using the three scanning protocols (p>0.05). There were no statistically significant differences between measurements in the 3 mm slice thickness and those in the 5 mm, 7 mm slice thickness (p>0.05). There were statistical differences in the 14 of the total 30 measured points in the 5 mm slice thickness and 22 in the 7mm slice thickness. Conclusion : The facial soft tissue thickness measurement using 3D images of 7 mm slice thickness is acceptable clinically, but those of 5 mm slice thickness is recommended for the more accurate measurement.