노화와 항산화효소의 역할에 관한 고찰

양미경(Yang Mi Kyong) 한국인체미용예술학회 2001 한국인체미용예술학회지 Vol.2 No.1

  In organisms, oxygen is essential but has a deleterious effects. Deleterious effects of oxygen is production of reactive oxygen species(ROS), for example superoxide radical(O₂?), hydrogen peroxide(H₂O₂), hydroxyl radical(OH.). But organisms produce antioxidants autonomically for recover the oxygen toxicity. Especially superoxide dismutase(SOD), catalase and glutathione peroxidase(GSH-PX) have a major roles against reactive oxygen species in organisms. Also reactive oxygen species induce many diseases. It is well understanding facts that ageing, cancer and arteriosclerosis occur by reactive oxygen species. Present antioxidants and reactive oxygen species were considered important in the field of biology, medicine, pharmacology, sitology, agriculture, toxicology, environment and many others. If we know the processes of production and mechanisms of reactive oxygen species, toxic effects of radicals will be reduce dramatically in living organisms. So understanding the mechanisms of response and processes of production is essential.

Mouse 신장에서 Azide가 반응성 산소에 의한 독성에 미치는 영향

곽상택,권태우,장현정,백광진,권년수,이희성 중앙대학교 의과대학 의과학연구소 1993 中央醫大誌 Vol.18 No.3

An increased production of reactive oxygen species has been postulated as a major pathogenic factor in the tissue damage occurring in high oxygen environment. Azide could enhance the oxygen toxicity by inhibiting superoxide dismutase and catalase, enzymes which remove reactive oxyge species. Mice were treated with azide (8.1 ㎎/㎏ body weight), and placed in a chamber saturated with 100% O_2 for 3, 6, 12, 24, 48 or 72 h. Superoxide radical generation, and activities of xanthine oxidase, superoxide dismutase and catalase in homogenate of the mouse kidney were measured. Superoxide radical generation was enhanced after exposing mice to azide/100% O_2, and reached to a maximum at 24 h. The elevated activity of cytosolic Cu, Zn-superoxide dismutase by the azid/oxygen treatment was sustained up to 12 h. Mitochondrial Mn-super oxide dismutase was slowly induced by the azide/oxygen treatment and was continuously increased until 72 h of exposing 100% o_2, while treatmet with neither azide nor oxygen alone enhanced the enzyme activity. Change of the catalase activity was not observed in the mouse kidney treated with azide and/or 100% oxygen. Xanthine oxidase activity was markedly decreased by the azide/oxygen treatmet. These reslts suggested that superoxide radicals generated in high oxygen tension were originated mainly from mitochondria, not from xanthine oxidase-catalyzed reaction. Thus, mitochondrial Mn-superoxide dismutase was induced to remove the superoxide radicals effectively.

Nitroprusside가 인간정자의 생존력, 운동성, Reactive Oxygen Species 발생에 미치는 영향

민부기,이희민,김기석,이희섭,김흥곤,홍기연,이봉주,Min, Bu-Kie,Lee, Hee-Min,Kim, Ki-Seok,Lee, Hee-Sup,Kim, Heung-Gon,Hong, Gi-Youn,Lee, Bong-Ju 대한생식의학회 1996 Clinical and Experimental Reproductive Medicine Vol.23 No.3

Objective: To analyze the direct effect of nitre oxide, generated from sodium nitroprusside, on sperm motility and reactive oxygen species. Design: Human sperm samples were treated to allow swim-up and washing. And the samples were devided into four aliquots. Each aliquot was incubated with either concentration at 0, 100nM, $10{\mu}M$, 1mM of nitroprusside. Intervention: Samples were measured chemiluminosence for reactive oxygen species of each aliquot with concentrations at 0, 100nM, $10{\mu}M$, 1mM of nitroprusside at allowing swim-up and washing of sperm. Main Outcome Measures: Percent motion parameters and viability were asse-ssed at 0, 3, 6, 12, 24 hours incubation. Results: The percent viablity was lower slightly in control group (50.2%) than that in sperm treated with 100nM of nitroprusside(57.5%) at 24 hours after incubation, while was reduced significantly in sperm with concentra-tion of $10{\mu}M(42.1%)$ and 1mM(21.3%)of nitroprusside at 6 hours after incubation. And the sperm treated with 1mM of nitroprusside was immotile totally at 6 hours after incubation. The straight line$(35.3{\pm}5.6%)$, the rapid forward$(37.2{\pm}6.4%)$ and the weak curvilinear velocity$(9.6{\pm}2.4%)$were more favorable comparing with those ($32.4{\pm}4.2%$, $30.0{\pm}7.8%$ and $18.0{\pm}4.6%$ respectively) in control group at 3 hours after incubation, but reduced significantly in sperm treated with $10{\mu}M$ and 1mM of nitroprusside. The levels of reactive oxygen species in control(700 c.p.m.) is lower significantly than that in each experimental groups of sperm treated with nitroprusside. And the levels of reactive oxygen species were 2200 c.p.m. in 100nM, 6200c.p.m. in $1{\mu}M$ and 12800c.p.m. in 1mM respectively. Conclusion: These results suggested that the concentration of 100nM of nitroprusside on sperm is beneficial to the maintanance of viablity and motile velocity, but detriment in high concentration of $10{\mu}M$ or 1mM of nitroprusside.

Allopurinol modulates reactive oxygen species generation and Ca²⁺ overload in ischemia-reperfused heart and hypoxia-reoxygenated cardiomyocytes

Kang, Seok-Min,Lim, Soyeon,Song, Heesang,Chang, Woochul,Lee, Sunju,Bae, Sang-mee,Chung, Ji Hyung,Lee, Hakbae,Kim, Ho-Gyoung,Yoon, Deok-Hyo,Kim, Tae Woong,Jang, Yangsoo,Sung, Jae-Mo,Chung, Nam-Sik,Hwan Elsevier 2006 european journal of pharmacology Vol.535 No.1

<P><B>Abstract</B></P><P>Myocardial oxidative stress and Ca<SUP>2+</SUP> overload induced by ischemia-reperfusion may be involved in the development and progression of myocardial dysfunction in heart failure. Xanthine oxidase, which is capable of producing reactive oxygen species, is considered as a culprit regarding ischemia-reperfusion injury of cardiomyocytes. Even though inhibition of xanthine oxidase by allopurinol in failing hearts improves cardiac performance, the regulatory mechanisms are not known in detail. We therefore hypothesized that allopurinol may prevent the xanthine oxidase-induced reactive oxygen species production and Ca<SUP>2+</SUP> overload, leading to decreased calcium-responsive signaling in myocardial dysfunction. Allopurinol reversed the increased xanthine oxidase activity in ischemia-reperfusion injury of neonatal rat hearts. Hypoxia-reoxygenation injury, which simulates ischemia-reperfusion injury, of neonatal rat cardiomyocytes resulted in activation of xanthine oxidase relative to that of the control, indicating that intracellular xanthine oxidase exists in neonatal rat cardiomyocytes and that hypoxia-reoxygenation induces xanthine oxidase activity. Allopurinol (10 μM) treatment suppressed xanthine oxidase activity induced by hypoxia-reoxygenation injury and the production of reactive oxygen species. Allopurinol also decreased the concentration of intracellular Ca<SUP>2+</SUP> increased by enhanced xanthine oxidase activity. Enhanced xanthine oxidase activity resulted in decreased expression of protein kinase C and sarcoendoplasmic reticulum calcium ATPase and increased the phosphorylation of extracellular signal-regulated protein kinase and p38 kinase. Xanthine oxidase activity was increased in both ischemia-reperfusion-injured rat hearts and hypoxia-reoxygenation-injured cardiomyocytes, leading to reactive oxygen species production and intracellular Ca<SUP>2+</SUP> overload through mechanisms involving p38 kinase and extracellular signal-regulated protein kinase (ERK) via sarcoendoplasmic reticulum calcium ATPase (SERCA) and protein kinase C (PKC). Xanthine oxidase inhibition with allopurinol modulates reactive oxygen species production and intracellular Ca<SUP>2+</SUP> overload in hypoxia-reoxygenation-injured neonatal rat cardiomyocytes.</P>

Role of reactive oxygen species in apoptosis induced N-ethylmaleimide in HepG2 human hepatoblastoma cells

Kim, Jung-Ae,Kang, Young Shin,Park, Seung Hee,Kim, Hae Won,Cho, Soon-Yeong,Lee, Yong Soo 영남대학교 약품개발연구소 2002 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

We have previously reported that N-ethylmalcimide induces apoptosis through activation of K^+, Cl^- -cotransport in HepG2 human hepatoblastoma cells. In this study, we investigated the role for reactive oxygen species as a mediator of the apoptosis induced by N-ethylmaleimide. N-ethylmaleimide induced a significant elevation of intracellular level of reactive oxygen species. Treatment with antioxidants (N-acetyi cystine, N,N^3-diphenyl-p-phenylenediamine) which markedly suppressed generation of reactive oxygen species, significantly inhibited the N-ethylmaleimide-induced activation of K^+, Cl^- -contransport and apoptosis. Inhibitors of NADPH oxidase (diphenylene iodonium, apocynin, ^1)-(+)-neopterine) also significantly blunted the generaton of reactive oxygen species, activation of K^+, Cl^- -cotransport and apoptosis induced by N-ethylmaleimide. These results suggest that reactive oxygen species generated through activation of NADPH oxidase may play a role in the N-ethylmaleimide-induced stimulation of K^+, Cl^- -contransport and apoptosis in HepG2 cells.

Licochalcone A Enhances Geldanamycin-Induced Apoptosis through Reactive Oxygen Species-Mediated Caspase Activation

Kim, Yun Jeong,Jung, Eun Byul,Myung, Soon Chul,Kim, Wonyong,Lee, Chung Soo S. Karger AG 2013 Pharmacology Vol.92 No.1

<P>Abstract</P><P><B><I>Background and Purpose:</I></B> Geldanamycin and licochalcone A induce apoptosis in cancer cells. However, whether the combination of geldanamycin and licochalcone A-induced apoptosis in epithelial ovarian cancer cells is mediated by the formation of reactive oxygen species, leading to the activation of apoptotic caspase, has not been studied. <B><I>Experimental Approach:</I></B> Using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3, we investigated the promoting effect of licochalcone A on geldanamycin-induced apoptosis. <B><I>Results:</I></B> Geldanamycin induced changes in apoptosis-related protein levels, loss of the mitochondrial transmembrane potential, release of cytochrome <I>c</I>, activation of caspases, cleavage of PARP-1, formation of reactive oxygen species and depletion of glutathione (GSH). Licochalcone A enhanced geldanamycin-induced apoptosis-related protein activation, formation of reactive oxygen species, caspase activation and cell death. The combined effect was inhibited by the addition of oxidant scavengers. <B><I>Conclusions:</I></B> Licochalcone A may potentiate the apoptotic effect of geldanamycin on ovarian carcinoma cell lines by the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway. The apoptosis-promoting effect of licochalcone A may be mediated by its stimulatory action on the formation of reactive oxygen species and the depletion of GSH, which results in the activation of caspases.</P><P>© 2013 S. Karger AG, Basel</P>

Therapeutic effect of magnesium lithospermate B on neointimal formation after balloon-induced vascular injury

Hur, K.Y.,Seo, H.J.,Kang, E.S.,Kim, S.H.,Song, S.,Kim, E.H.,Lim, S.,Choi, C.,Heo, J.H.,Hwang, K.C.,Ahn, C.W.,Cha, B.S.,Jung, M.,Lee, H.C. North-Holland ; Elsevier Science Ltd 2008 european journal of pharmacology Vol.586 No.1

Vascular smooth muscle cell (VSMC) proliferation and migration in response to platelet-derived growth factor (PDGF) play an important role in the development of atherosclerosis and restenosis. Recent evidence indicates that PDGF increases intracellular levels of reactive oxygen species in VSMCs and that both PDGF-induced VSMC proliferation and migration are reactive oxygen species-dependent. Danshen is a representative oriental medicine used for the treatment of vascular disease. Previously, we reported that magnesium lithospermate B, an active component of Danshen, is a potent antioxidant. Thus we investigated the therapeutic potential of magnesium lithospermate B in neointimal formation after carotid artery injury in rats along with its effects on the PDGF signaling pathway for stimulating VSMC proliferation and migration in vitro. PDGF is dimeric glycoprotein composed of two A or two B chains. In this study, we used PDGF-BB, which is one of the isoforms of PDGF (i.e., PDGF-AA, PDGF-BB, and PDGF-AB). Our results demonstrated that magnesium lithospermate B directly scavenged reactive oxygen species in a xanthine/xanthine oxidase system and reduced PDGF-BB-induced intracellular reactive oxygen species generation in VSMCs. In a rat carotid artery balloon injury model, magnesium lithospermate B treatment (10 mg/kg/day, i.p) showed a significant effect on the prevention of neointimal formation compared with vehicle treatment. In cultured VSMCs, magnesium lithospermate B significantly attenuated PDGF-BB-induced cell proliferation and migration as measured by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay and transwell migration assays, respectively. Further, magnesium lithospermate B inhibited PDGF-BB-induced phosphorylation of phospatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways by scavenging reactive oxygen species. Together, these data indicated that magnesium lithospermate B, a potent reactive oxygen species scavenger, prevented both injury-induced neointimal formation in vivo and PDGF-BB-induced VSMC proliferation and migration in vitro, suggesting that magnesium lithospermate B may be a promising agent to prevent atherosclerosis and restenosis following angioplasty.

플라보노이드 luteolin이 세포자멸사 관련 단백질 활성 억제를 통해 6-hydroxydopamine 세포독성에 미치는 억제효과

이선화,강진호,한정호,김두응,이정수 대한신경과학회 2012 대한신경과학회지 Vol.30 No.4

Background: Flavonoid luteolin has been shown to exhibit cell protective effect. However, it is still uncertain whether the effect of luteolin on cellular toxicity of the parkinsonian toxin 6-hydroxydopamine is mediated by apoptosis-related protein activation. Methods: In differentiated PC12 cells exposed to 6-hydroxydopamine in combination with luteolin, we observed the apoptosis-related protein activation, nuclear damage, formation of reactive oxygen species and cell death. Results: 6-Hydroxydopamine caused apoptosis by inducing a decrease in Bid, Bcl-2, Bcl-xL and survivin levels, increase in Bax levels, cytochrome c release and activation of caspases. Treatment with luteolin reduced changes in the apoptosis-related protein levels, formation of reactive oxygen species, nuclear damage and cell death. Conclusions: Luteolin may reduce the 6-hydroxydopamine-induced apoptosis in differentiated PC12 cells by suppressing the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway, leading to caspase activation. The preventive effect of luteolin may be associated with its inhibitory effect on the production of reactive oxygen species. Luteolin may attenuate the oxidative stress and mitochondrial dysfunction-induced neuronal cell death take place in Parkinson’s disease. Background: Flavonoid luteolin has been shown to exhibit cell protective effect. However, it is still uncertain whether the effect of luteolin on cellular toxicity of the parkinsonian toxin 6-hydroxydopamine is mediated by apoptosis-related protein activation. Methods: In differentiated PC12 cells exposed to 6-hydroxydopamine in combination with luteolin, we observed the apoptosis-related protein activation, nuclear damage, formation of reactive oxygen species and cell death. Results: 6-Hydroxydopamine caused apoptosis by inducing a decrease in Bid, Bcl-2, Bcl-xL and survivin levels, increase in Bax levels, cytochrome c release and activation of caspases. Treatment with luteolin reduced changes in the apoptosis-related protein levels, formation of reactive oxygen species, nuclear damage and cell death. Conclusions: Luteolin may reduce the 6-hydroxydopamine-induced apoptosis in differentiated PC12 cells by suppressing the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway, leading to caspase activation. The preventive effect of luteolin may be associated with its inhibitory effect on the production of reactive oxygen species. Luteolin may attenuate the oxidative stress and mitochondrial dysfunction-induced neuronal cell death take place in Parkinson’s disease.

Reactive Oxygen Species Modulator 1 as a Novel Predictive and Prognostic Biomarker for EGFR-mutant Lung Adenocarcinoma Treated with Targeted Therapy

( Seung Hyeun Lee ),( Ji-youn Sung ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.0

Introduction Reactive oxygen species modulator 1 (Romo1) is a novel protein that regulates the production of intracellular reactive oxygen species. Romo1 has been shown to be associated with poor survival in various clinical settings for the treatment of lung cancer. In this study, we evaluated whether tissue Romo1 expression was associated with clinical outcomes in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma treated with tyrosine kinase inhibitors (TKIs). Materials and Methods Romo1 expression in tumor tissues was examined by immunohistochemistry and evaluated by histologic score. Univariate and multivariate analyses were performed to identify the clinicopathologic parameters, including Romo1 expression, which may be associated with progression-free survival (PFS), overall survival (OS), and incidence of secondary T790M mutation. Results A total of 96 tumor specimens were analyzed. With the cut-off value of 200, 71 (74.0%) and 25 (26.0%) patients were classified into low and high Romo1 groups, respectively. The median PFS of the high Romo1 group was significantly shorter than that of the low Romo1 group (13.1 vs 19.9 months, p = 0.0165). The median OS of the high Romo1 group was also significantly shorter than that of the low Romo1 group (19.8 vs 37.0 months, p = 0.0006). Multivariate analyses showed that high Romo1 expression was independently associated with both poor PFS (hazard ratio [HR] = 2.48, 95% confidence interval [CI]: 1.35-4.56, p = 0.0034) and poor OS (HR = 3.17, 95% CI: 1.57-6.41, p = 0.0013). In addition, the frequency of secondary T790M mutation after TKI failure was significantly lower in the high Romo1 group than the low Romo1 group (16.7% vs. 38.3%, p = 0.0369). Conclusion Romo1 overexpression was associated with poor response to treatment and short survival in patients treated with EGFR-TKIs, suggesting Romo1 could be a potential predictive and prognostic biomarker for this patient population.

Influence of reactive oxygen species on the sterilization of microbes

Uhm, H.S.,Choi, E.H.,Cho, G.S.,Hwang, D.H. Elsevier 2013 Current Applied Physics Vol.13 No.suppl1

The influence of reactive oxygen species on living cells, including various microbes, is discussed. A sterilization experiment with bacterial endospores reveals that an argon-oxygen plasma jet very effectively kills endospores of Bacillus atrophaeus (ATCC 9372), thereby indicating that oxygen radicals are the key element of sterilization. Ozone in acidic water also kills endospores of B. atrophaeus very effectively, demonstrating the capability of cleaning a large surface area contaminated by toxic biological agents. The viable microbe numbers after the contact with acidic ozone water directly correlate with increase in the ozone decay time in water after lowering the pH value of water from pH = 7 to 4 indicating that acidic ozone water is an effective means of sterilizing microbes. However, advanced cells such as fertilized eggs were not greatly influenced by the acidic ozone water. Also, both human and canine cells after treatment with the acidic ozone water prospered without showing signs of stress due to ozone in acidic water. This study suggests that antioxidant enzymes such as superoxide dismutase can be developed in the advanced cells to protect themselves from attacks by reactive oxygen species. Meanwhile, the advanced cells utilize oxygen by certain enzymes, proliferating life on earth.