백서 혈관평활근 세포에서 α-Lipoic acid가 PAI-1 발현, 세포의 증식, 주유능 및 신생내막 형성억제에 미치는 효과

신동우,이동욱,이상준,김혜순,강효경,안종덕,이인규 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6

연구배경:당뇨병의 혈관 합병증의 발생에 있어서 산화스트레스는 중요한 역할을 하는 것으로 알려져 있다. 혈관 평활근세포에서 고혈당은 안지오텐신Ⅱ와 더불어 활성산소족(ROS)을 증가시키며, 산화스트레스에 민감한 전사인자들을 활성화시켜 동맥경화증을 유발하는 것으로 알려져 있다. 이에 저자들은 항산화제로 알려진 알파­리포산이 혈관 평활근세포의 증식속도와 이주에 미치는 영향과 PAI­1발현에 미치는 영향을 조사하였고 이와 동시에 백서의 혈관 손상 모델을 이용하여 알파­리포산이 신생내막 증식을 억제시킬 수 있는지를 알아보았다. 방법:In vitro 실험은 백서의 대동맥 평활근세포를 고농도의 포도당(22mM)과 100nM의 안지오텐신Ⅱ로 4시간 배양하였다. 알파­리포산을 처리 후, PAI­1 mRNA의 발현을 보기 위해 노던 블롯을 시행하였고 평활근세포의 유주능과 증식속도에 미치는 영향을 보기 위해 성장속도의 유주능 분석을 시행하였다. 또한 평활근세포의 유주능에 NF­μB 경로가 미치는 영향을 보기 위해 겔 지연 분석과 NF­μB 보고 유전자 분석을 시행하였다. In vivo 실험으로 백서의 혈관손상 모델을 이용하여 알파­리포산 처리 후 혈관의 신생내막 두께를 비교하였다. 결과:In vitro 실험에서 고농도 포도당과 안지오텐신Ⅱ에 의해 유도된 PAI­1 mRNA 발현증가는 알파­리포산 처리에 의하여 용량에 비례하여 억제되었다(p<0.05). 알파­리포산 처리로 혈관 평활근세포의 유주능은 유의하게 억제되었으나(p<0.01),증식속도는 유의하게 억제되지 않았다. 또한 알파­리포산 처리로 NF­μB 발현도 유의하게 억제되었다(p<0.01). In vivo 실험에서 알파­리포산을 주입한 군에서 혈관손상에 의한 신생내막의 증식이 유의하게 억제되는 것을 보여주었다(p<0.01). 결론:알파­리포산은 백서의 대동맥 평활근 세포의 증식속도는 억제하지 못했으나 유주능은 유의하게 억제하였으며, 혈관 손상 모델에서 신생 내막 증식도 유의하게 억제함을 확인할 수 있었다. 이러한 작용은 알파­리포산에 의한 NF­μB 경로의 억제와 연관이 있는 것으로 사료된다. Background : Exposure to large amounts of glucose causes a characteristic dysfunction and morphologic changes of the endothelium by an increased production of reactive oxygen species(ROS) in diabetes. The plasminogen activator inhibitor-1(PAI-1), which modulates fibrinolysis and cell migration may influence proteolysis and neointimal formation in vascular smooth muscle cells(VSMC). Antioxidants have been proposed to inhibit multiple proatherogenic events. This study investigated the effect of α-lipoic acid on PAI-1 expression and VSMC proliferation and migration both in vivo and in vitro. Methods : In the in vitro study, cultured rat aortic smooth muscle cells(RASMC) were incubated in a medium containing high glucose (22 mM) and 100 nM angiotensin Ⅱ for 4 hour. After α-lipoic acidtreatment, a -migration and growth assay of the RASMC, and a gelmobility shift assay and reportergene analysis for nuclear factor- иB(NF- иB) and northern blot analysis for PAI-1 were performed. In the in vivo study, the effect of α-lipoic acid on neointimal hyperplasia in a rat carotid balloon injury model was evaluated. Results : RASMC migration was inhibited significantly by α-lipoic acid (p<0.01), but their prolife ration was not inhibited. The NF-иB DNA binding activity and NF-иB promoter activity was inhibited by α-lipoic acid significantly (p<0.01). α-lipoic acid inhibited PAI-1 mRNA expression by high glucose and angiotensin Ⅱ in dose dependent manner (p<0.05). In the rat carotid artery balloon injury model, neointimal formation was reduced by α-lipoic acid treatment in a dose dependent manner significantly (p<0.01). Conclusion : α-lipoic acid suppresses migration, but not prolife ration in RASMC. α-lipoic acid also reduce neointima formation in a rat carotid balloon injured model. This effect might be related to the blocking of NF-иB which increase the expression of the genes associated with atherosclerosis including TNF-α, IL-1, IL-6, endothelin-1, MCP-1, VCAM-1, ICAM-1, E-selectin, tissue factor(J Kor Diabetes Asso 25:446~459, 2001).

+61A>G polymorphism in the <i>EGF</i> gene does not increase the risk of lung cancer

KANG, Hyo-Gyoung,CHOI, Jin Eun,LEE, Won Kee,KAM, Sin,CHA, Sung Ick,KIM, Chang Ho,JUNG, Tae Hoon,PARK, Jae Yong Blackwell Publishing Asia 2007 Respirology Vol.12 No.6

<P>Background and objectives: </P><P>Epidermal growth factor (EGF) plays an important role in tumourigenesis by binding with its receptor, EGFR. Variations in the DNA sequence in the <I>EGF</I> gene can lead to an alteration in EGF production and/or activity, which can affect an individual's susceptibility to lung cancer. To test this hypothesis, this study examined the association between the +61 A>G polymorphism in the 5′-untranslated region of the <I>EGF</I> gene and the risk of lung cancer in a Korean population.</P><P>Methods: </P><P>The <I>EGF</I>+61 A>G genotype was determined in 432 lung cancer patients and 432 healthy age- and gender-matched control subjects.</P><P>Results: </P><P>The +61 AA and +61 AG genotypes were not significantly associated with the risk of lung cancer compared with the +61 GG genotype (adjusted OR = 1.02, 95% CI: 0.77–1.37; and adjusted OR = 0.81, 95% CI: 0.51–1.29, respectively). In addition to the reference model, the <I>EGF</I>+61 A>G polymorphism had no significant association with the risk of lung cancer under both dominant and recessive models for the +61A allele (adjusted OR = 0.98, 95% CI: 0.74–1.29; and adjusted OR = 0.80, 95% CI: 0.51–1.24, respectively).</P><P>Conclusion: </P><P>These results suggest that the <I>EGF</I>+61 A>G polymorphism may not significantly affect the susceptibility to lung cancer in the Korean population.</P>

Influence of Microstructures on Mechanical Properties of Al-Si-Cu-Mg Cast Alloys

Kang, Hyo Gyoung,Choi, Chang Ock,Ogi, Keisaku 동아대학교 생산기술연구소 2000 生産技術硏究所硏究論文集 Vol.5 No.1

A commercial Al-Si-Cu base alloy (JIS AC4B) and the similar compositions of pure alloys with 0 to 0.7%Fe were solidified at the cooling rate of 2.7 to 14.4K/s. Tensile tests and quantitative microstructure analysis were performed on the as cast specimens and T_6specimens. Tensile strength (бB) increased as the microstructure became finer. бB rose linearly with decreasing of secondary dendrite arm spacing(DAS) of primary α , while the modification of eutectic Si with Sr had a smaller effect. The crack propagated along dendrite arms and the fracture surface exhibited a structure whose coarseness was close to DAS. Fe-rich intermetallic compounds took the acicular and chinese script type shapes. Higher cooling rate and more Sr addition promoted the crystallization of chinese type one. The Fe-rich compounds decreased the elongation, though they tended to raise the yield strength. TEM analysis revealed that the aging process was influenced by eutectic Si and minor elements, however the these phenomena may have little influence on tensile properties.

Effects of Alloy Compositions (Cu and Mg ) and Aging Conditions on the Age Hardening Characteristics of Al-Si-Cu-Mg Cast Alloys

Kang, Hyo-Gyoung,Choi, Chang-Ock,Ogi, Keisaku 동아대학교 환경문제연구소 1999 硏究報告 Vol.22 No.2

TEM analysis was applied to the investigation on age hardening processes of a commercial JIS ACAB alloy and the similar compositions of pure N-Si-Cu and Al-Si-Cu-Mg cast alloys. A series of alloy specimens were solution treated at 773K for l0hr and subsequently aged at 433K and 473K for l0min to 10⁴min. The typical hardness-aging time relations are obtained on each alloy specimen. The maximum hardness of specimen aged at 433K becomes larger from Hv95 to Hv152 as the Mg content of alloy increases from 0 to 0.43mass%. TEM reveals many dislocations around eutectic Si particles, which should be introduced into aphase during quenching from solution treatment emperature, because of the difference in the thermal expansion coefficient between α-natrix and eutectic Si. The formation of GP Zone is suppressed and the precipitation of θ' is promoted in the ternary 4-Si-Cu alloy, which contains higher density of dislocations. Many tiny particles of Mn-rich compound precipitate in the α matrix of solution-treated. AC4B alloy, which decrease the Cu content of a phase and the age-hardening ability of the alloy.

A Functional Polymorphism in CSF1R Gene Is a Novel Susceptibility Marker for Lung Cancer among Never-Smoking Females

Kang, Hyo-Gyoung,Lee, Shin Yup,Jeon, Hyo-Sung,Choi, Yi Young,Kim, Soyoun,Lee, Won Kee,Lee, Hyun Chul,Choi, Jin Eun,Bae, Eun Young,Yoo, Seung Soo,Lee, Jaehee,Cha, Seung Ick,Kim, Chang Ho,Lee, Myung Hoo LIPPINCOTT WILLIAMS WILKINS 2014 JOURNAL OF THORACIC ONCOLOGY Vol.9 No.11

Effects of Casting Conditions and Additions of Sr and Ti+B on Solidification Structures of Recycle Al-Si-Cu System Cast alloys

Kang, Hyo-Gyoung,Choi, Chang-Ock,Ogi, Keisaku 동아대학교 환경문제연구소 1999 硏究報告 Vol.22 No.2

The effects of cooling rate and additions of Sr and Ti-B on microstructural features such as grain size, dendrite arm spacing, morphologies of eutectic silicon and iron rich compound were investigated for the Al-6.55%Si-2.78% Cu-0.59%Fe-0.38%Mg-0.34%Mn alloy of ACAB type. This alloy solidified in the order of primary α, a+a-AlFeMnSi compound eutectic, α+Sieutectic, α+β-AlFeMnSi. a +Si+Mg₂Si and α+Si+Al₂Cu eutectic. The grain size, dendrite arm spacing, the size of eutectic silicon particles and the length of needle like β-AlFeMnSi decreased with increasing the cooling rate, and they were in linear relations on logarithmic scales. Addition of small amount of Ti-B remarkably refined grain size while it practically unaffected the other solidification structures At the cooling rate of 2.73K/s, 14.38K/s and 108.08K/s, the eutectic silicon crystals fully modified by adding Sr more than 60ppm, 20ppm and 5ppm, respectively. Addition of Sr and higher cooling rate tended to modify the needle like iron rich compounds to Chinese script type one. DSC analysis revealed that the Sr modification was accompanied by the characteristic changes in cooling curve.

IMT-2000용 주파수 대역에서 동작하는 VCO 구현에 관한 연구

정효경(Hyo Gyoung Jeong),강석엽(Suk Youb Kang),이기혁(Ki Hyuk Lee),박효달(Hyo Dal Park) 한국통신학회 1999 한국통신학회 학술대회논문집 Vol.1999 No.11

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>

온간 ECAP 법에 의해 제조된 5083 Al 합금의 미세조직과 기계적 특성

강석봉,강효경,김향욱,Bachelard, L . 대한금속재료학회(대한금속학회) 2001 대한금속·재료학회지 Vol.39 No.5

The microstructure and mechanical properties have been investigated on a commercial 5083 aluminum alloy processed by the equal-channel angular pressing (ECAP) at 473K. The microstructure of a single pass sample consisted of elongated subgrains. Increasing the number of pass led to very fine equilibrium grains having high angle grain boundaries. The 0.2% yield stress and hardness after a single pass increased greatly, and then kept constant with additional straining. On the other hand, the elongation to failure of a single pass sample decreased a little to compare with sample before ECAP, but there was no further reduction with additional straining. Recrystallization partially occurred in ECAPed 5083 aluminum alloy when annealed at 523K for 1 hr, and completely finished when annealed only at 573K for 1 hr. With increasing the number of pass, the onset temperature of recrystallization decreased and the rate of softening increased.

ECAP법에 의해 제조된 6061 알루미늄 합금의 미세조직과 기계적 특성에 미치는 기공온도의 영향

강효경,김형욱,강석봉 대한금속재료학회 2002 대한금속·재료학회지 Vol.40 No.2

Equal Channel Angular Pressing(ECAP) was carried out on the 6061 aluminum alloy at room temperature, 373K, 423K, and 473K. The microstructures and mechanical properties of specimens pressed at different temperatures and cycles were investigated. All specimens pressed at different temperatures show ultra fine-grained microstructures with the average grain size less than 0.5 ㎛ and dislocation cell structure. When the pressing temperature increased higher than 423K, the tensile strength of the specimens decreased and the total elongation increased. In case of specimens pressed for 4 cycles at 473K, the fraction of grains having high angle grain boundaries is higher than that pressed at room temperature. The specimen pressed for 4 cycles at room temperature shows higher increase of the 0.2% yield strength, ultimate tensile strength and hardness, and much higher decrease of work hardening index.