Prostaglandin A₂-induced Apoptosis is Not Inhibited by Heme Oygenase-1 in U2OS Cells

Kyoung-Won Ko(고경원),Sun-Young Lee(이선영),Ji-Hyun Ahn(안지현),Jaetaek Kim(김재택),In-Kyung Kim(김인경),Ho-Shik Kim(김호식) 한국생명과학회 2008 생명과학회지 Vol.18 No.11

Prostaglandin A₂ (PGA₂)는 사람 골육종 세포인 U2OS 세포주에서 apoptosis와 heme oxygenase (HO)-1의 발현을 함께 유도하였다. PGA₂에 의한 apoptosis는 HO-1의 과도한 발현이나 HO-1에 대한 small interfering RNA에 의한 발현저하에 의하여 변동되지 않았으나 H₂O₂에 의한 세포사망은 HO-1의 발현 수준에 반비례하여 변동되었다. 또한 thiol antioxidant인 N-acetyl-L-cysteine (NAC)은 PGA₂에 의한 세포사망과 HO-1의 발현 증가를 모두 차단하였지만, non-thiol antioxidant인 butylated hydroxyanisole (BHA)과 ascorbic acid는 세포사망과 HO-1의 발현 유도를 차단하지 않았다. 이와 같은 결과들은 PGA₂는 산화성 손상에 의해서가 아니라 PGA₂의 thiol-reactivity에 의하여 apoptosis와 HO-1의 발현을 유도하며, HO-1의 발현은 PGA₂에 의한 apoptosis와는 독립적인 현상이거나 기능적으로 apoptosis 유도의 하부에 위치하고 apoptosis의 진행에는 기여하지 않을 것이라는 것을 시사해 준다. Prostaglandin A₂ (PGA₂), one of cyclopentenone PGs, induced both apoptosis and heme oxygenase (HO)-1 expression in U2OS cells. PGA₂-induced apoptosis was not perturbed by either over-expression or knock-down of HO-1, whereas H₂O₂-induced cell death was inversely modulated by the expression level of HO-1. In addition, N-acetyl-L-cysteine (NAC), a thiol antioxidant, blocked both apoptosis and HO-1 expression induced by PGA₂. But, non-thiol antioxidants like butylated hydorxyanisole (BHA) and ascorbic acid did not block either apoptosis or HO-1-induction. Taken together, these results suggest that PGA₂ induces both apoptosis and HO-1 expression, which are critically related to the thiol-reactivity of PGA₂, but not oxidative stress, and HO-1 expression may be independent or functionally located downstream of apoptosis by PGA₂ without contribution to apoptosis progression.

Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

( Sun-uk Bak ),( Suji Kim ),( Hae-jun Hwang ),( Jung-a Yun ),( Wan-sung Kim ),( Moo-ho Won ),( Ji-yoon Kim ),( Kwon-soo Ha ),( Young-guen Kwon ),( Young-myeong Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.2

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1^+/-cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. [BMB Reports 2017; 50(2): 103-108]

중소기업의 동반성장 전략과 기업성과의 인과 관계

반완호(Ban Won Ho) 한국산학기술학회 2018 한국산학기술학회논문지 Vol.19 No.12

1960년대 이후 대기업은 한국 경제에서 기업 중심의 고도성장으로 지금까지 발전해 온 반면 중소기업은 대기업의 하부구조로서의 시스템으로써 한국경제를 이끌어왔다. 최근 기업 환경의 글로벌화에 따라 개별기업 간 경쟁에서 기업 네트워크 간 경쟁구조로 변화함에 따라 개별기업의 자체 역량보다는 기업 간 협력네트워크의 역량이 중요시 되고 있다. 따라서본 연구에서는 중소기업의 협력활동을 통한 동반성장 전략 요소가 기업성과에 어떠한 영향을 미치는지 살펴보고자 하였다. 본 연구는 2018년 3월 2일부터 5월 17일까지 국내 대기업과 협력경험이 있는 중소기업 근무자를 대상으로 하였고, 총 515명의 설문지에 대한 자료가 분석에 사용되었다. 분석방법은 SPSS 22.0과 AMOS 18.0을 사용하여 탐색적 요인분석, 확인적 요인분석, 신뢰도 분석, 상관분석, 구조방정식 모형을 실시하였다. 분석결과, 먼저 기업성과의 전략적 성과에 영향을 미치는 동반성장 전략요소는 목표일치성, 생산기술지원, 품질시스템으로 나타났다. 둘째, 기업성과의 재무적 성과에 영향을 미치는 동반성장 전략요소는 목표일치성, 품질시스템, 인센티브 연계로 나타났다. 본 연구의 결과를 통해 기업에 있어서 목표일치성, 생산기술지원, 품질시스템, 인센티브 연계 등과 같은 요소는 기업성과에 직접적인 영향을 미치는 중요한 인프라 요소임을 알 수 있었다. 반면, 공동지식창출과 같은 정보나 지식과 같은 요소는 그 자체로서 부가가치가 없고, 아직까지 기업성과에 영향을 미치기 어렵다는 현실을 반영함을 시사한다. Since 1960’s, the large conglomerates of South Korea have grown due to the corporate-centered, fast-paced growth drive, while the small and medium-sized businesses supported the country’s economy as the subordinate structure of these conglomerates. Due to the globalization of the business environments, the focus of competition shifted from competitions between individual companies to one between networks of companies. Therefore, more emphasis is now put on the capabilities of the cooperation networks between companies rather than the capabilities of individual companies. Therefore, in this study, the author examined the influence of the win-win growth strategy elements through cooperation with small and medium-sized businesses upon corporate performance. This study was conducted with the workers of small and medium-sized businesses that have previous cooperation experiences with South Korean conglomerates over the period from March 2 to May 17, 2018. For this, a total of 515 questionnaires were retrieves to obtain the data for analysis. The analysis was conducted using SPSS 22.0 and AMOS 18.0. The analytical processes that were taken included exploratory factor analysis, confirmatory factor analysis, confidence analysis, correlation analysis, and structural equation analysis model. The results of the analysis showed that, first of all, the win-win growth strategy factors that affected the strategic performance, which is a part of cooperate performance were, respectively, harmonization with the goals, production technical support, and quality system. Second, the win-win growth strategy factors that affected the financial performance, which is a part of corporate performance, turned out to be harmonization with the goals, quality system, and incentive. With the results of this study, it was shown that the elements such as harmonization with the goals, production technical support, quality systems, and incentives were key infrastructural factors that affected the corporate performance directly. On the other hand, its implication is that informative or knowledge-related factors, such as joint knowledge creation, do not have their own added values, while they are not too much likely to affect corporate performances for the moment.

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.

물류산업의 국민경제적 파급효과 분석

정동원 ( Dong Won Jeong ),한종호 ( Jong Ho Han ) 한국물류학회 2012 물류학회지 Vol.22 No.2

물류산업은 경제 발전에 중요한 역할을 담당하며, 산업경쟁력과 국가경쟁력을 결정하는 중요한 요소로 작용하고 있다. 본 논문에서는 산업연관분석을 이용하여 물류산업의 국민경제적 파급효과를 분석하고자 한다. 먼저 수요유도형 모형을 이용하여 물류산업의 타 산업 생산유발효과, 부가가치 유발효과, 취업유발효과를 살펴본다. 다음으로 상대적으로 복잡성 때문에 잘 사용되지 않았던 공급유도형 모형 및 레온티에프 가격모형을 적용하여 물류산업의 공급지장효과 및 물가파급 효과를 살펴본다. 이러한 분석은 모두 물류산업을 내생부문이 아닌 외생부문으로 다룸으로써 물류산업을 중심으로 이루어지게 된다. 주요 분석결과를 요약하면 다음과 같다. 물류산업의 1원 생산은 타 산업의 생산을 0.5104원만큼 유발하며, 타산업의 부가가가치를 0.1722원만큼 유발한다. 또한 물류산업의 10억원 생산은 타산업에서 2.2554명의 취업을 유발한다. 한편 물류산업에서 1원의 공급이 이루어지지 못할 때, 타 산업에서는 0.9387원의 생산차질이 발생하여 공급지장효과가 제법 큰 편이다. 마지막으로 물류산업의 가격이 10& 상승했을 때, 국민경제 전체적으로 미치는 물가파급효과는 0.0276%로 분석되었다. The logistics industry in Korea plays a major role in the national economy development and to make decision nation and industrial competitiveness, This study attempts to examine the economic impacts of the logistics industry using an inter-industry analysis, Specially, the study investigates production-inducting effect, value added inducing effect, and employment-inducing effect of the logistics industry based on demand-driven model. Moreover, the study deals with supply shortage effect and sectoral price effect by using supply-driven model and leontief price model, respectively, which have been rarely used because of their complications involved in computaiton. These analyses pay particular and close attention to the distribution industry by taking it as exogenous rather than endogenous. Some interesting findings emerge from the study. First, the production of 1.0 won in the logistics industry induces the production of 0.5104 won and the value-added of 0.1722 won in other industries. Second, the production of 1.0 billion won in the logistics industry causes the employment of 2.554 persons in other industries. Third, the supply shortage of 1.0 won in the logistics industry disables other industries to produce 0.9387 won. Finally, an increase of 10% in price level of the logistics industry raises the overall price level by 0.0276%.

Study of decreased melanin production through p53 by heme oxygenase-1 inhibitor in normal human melanocytes

( Hee Sun Lim ),( Sun A Jin ),( Jee Bum Lee ),( Seong Jin Kim ),( Seung Chul Lee ),( Young Ho Won ),( Sook Jung Yoon ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Heme oxygenase (HO)-1 is induced by oxidative stress and plays important roles in anti-apoptosis and the rapid growth of several solid tumors. p53 has a central role in skin pigmentation and may impact onmelanoma at all stages. However, there has been little study of HO-1 in relation with p53 on melanin production Objectives: To know the effect of HO-1 on melanogenesis through p53 in normal human melanocytes Methods: Human melanocytes (hM) were primarily cultured from foreskin. After incubation, cells were rinsed twice with PBS then transfection with p53 siRNA Results: Melanin content was detected with ELISA and Western blot analysis and RT-PCR of tyrosinase, MITF were performed after ZnPP treatment and p53 transfection. After ZnPP treatment, melanin content was decreased, and tyrosinase and MITF protein levels were decreased. Tyrosinase and MITF mRNA levels were also decreased. However, melanin content and tyrosinase and MITF protein levels were increased after CoPP treatment. After p53 transfection, HO-1 expression was decreased when HO-1 stimulator was treated. In addition, melanin content was decreased, and tyrosinase expression was decreased in Western blot analysis Conclusion: These results suggest that melanogenesis is inhibited by ZnPP by decreased melanin production, tyrosinase and MITF protein and mRNA levels. Furthermore, those inhibitory effects of ZnPP may be dependent on p53 in normal human melanocytes. Therefore, HO-1 may play an important role in melanogensis

The Antioxidant Effect of the Rhaponticum uniflorum Extracts on the Oxidative Stress in H₂O₂ induced Human Keratinocytes

So Hee Ahn,Won Yeoung Choi,Ji Won Jeong,Geon Woo Park,Su Yeon Kang,Eun Jeong Kim,Su Rim Sin,Eun Seo Jang,Gye Won Lee,Young Ho Cho 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

In this study, To investigate the antioxidant activities of Rhaponticum uniflorum extracts (RUE), we assessed scavenging activities on DPPH, ABTS radicals, and reducing power. The DPPH and ABTS radical scavenging activities (SC50) of RUE were 96.97±1.19 μg/mL and 31.26±0.13 μ g/mL, respectively, and the reducing power significantly increased dose-dependent manner. To study the antioxidant effecters of RUE in H₂O₂ induced human keratinocytes, expression of Nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by Western blot and qRT-PCR. RUE induced the expression of HO-1, a critical target enzyme of Nrf2, in a concentration-dependent manner. The expression of HO- 1 mRNA was also induced in H₂O₂-treated HaCaT cells but no significant difference in the level of HO-1 mRNA was observed. Taken together, these results suggest that RUE may be useful as a potential ingredient for anti-aging products.

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.

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.

Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Choi, Seunghwan,Kim, Joohwan,Kim, Ji-Hee,Lee, Dong-Keon,Park, Wonjin,Park, Minsik,Kim, Suji,Hwang, Jong Yun,Won, Moo-Ho,Choi, Yoon Kyung,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11

<P>Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the <I>eNOS</I> mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of <I>eNOS</I> mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and <I>N</I>-acetylcysteine prevented H<SUB>2</SUB>O<SUB>2</SUB>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.</P>