FK506이 T 림프구 사멸에서 활성산소 생성에 미치는 영향

이호균(Ho Kyun Lee),정상영(Sang Young Chung),최수진나(Soo Jin Na Choi) 대한외과학회 2009 Annals of Surgical Treatment and Research(ASRT) Vol.77 No.5

Purpose: Tacrolimus (FK506) has been widely used as an immunosuppressant in organ transplanted recipients to suppress organ rejection phenomenon. We investigated the role of oxidative stress and heme oxygense-1 by FK506 on human Jurkat T cells. Methods: The cells viability was examined by DAPI stain, enzyme activity of caspase family proteins, and western blotting for Baks, PUMA, iNOS, HO-1. Cells were cultured in the absence or presence of CoPPIX or ZnPPIX and the fluorescence intensity was analyzed using a flow cytometry. Results: Treatment with FK506 increased the generation of reactive oxygen species (ROS), including hydrogen peroxide and superoxide anion, and NO in Jurkat cells in a dose-dependent manner. Immunohistochemistry and Western blot analysis data revealed the hemoxygenase-1 (HO-1) was induced by the addition of FK506 in Jurkat cells. Induction of CoPP, HO-1 inducer, resulted in decreased intracellular H₂O₂ and NO concentrations. Instead ZnPP, an HO-1 competitive inhibitor did it reversely. In addition, ZnPP regulates iNOS protein synthesis by inhibition of HO-1. Conclusion: Increase of HO-1 expression would induce to decrease the intracellular H₂O₂ and NO concentrations. Also, HO-1 would regulate iNOS protein synthesis. Consequently, we can expect the regulation of HO-1 expression with concomitants use of FK506 to suppress organ rejection phenomenon by enhancing apoptosis.

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>

염증성 피부질환 개선 기능 소재로서 둥근전복(Haliotis discus) 유래 항균펩타이드 Ab4-7의 항염증 효과

최수철 ( Soo-cheol Choi ),서정길 ( Jung-kil Seo ),황준호 ( Joon-ho Hwang ),이기영 ( Ki-young Lee ),이인아 ( In-ah Lee ) 대한화장품학회 2020 대한화장품학회지 Vol.46 No.2

서해안에 서식하는 해양생물인 전복은 항산화 및 항염증 효과가 있으며, 항생제 개발 및 화장품 원료 등 다양한 산업에 활용될 수 있는 잠재력을 가진 자원이다. 본 연구에서 우리는 서해안의 다양한 해양 생물중에서 전복을 선택하였으며, 전복에서 분리한 항균펩타이드(AMP)를 이용하여 항균펩타이드 유도체인 Ab4-7를 규명하고 생리활성을 연구하였다. Ab4-7의 항염증 효능을 확인하기 위해 염증이 유도된 RAW 264.7에 Ab4-7을 처리한 결과, 염증성 사이토카인, TLR4, TNF-α, IL-1β, COX-2, iNOS 등을 억제하고 항산화와 관련된 유전인자인 HO-1의 mRNA 발현을 증가시켰다. Ab4-7의 강력한 항산화 및 항염증 효과를 바탕으로, 염증이 유도된 RAW 264.7 세포에서 Ab4-7이 extrocellular matrix metalloproteinase (ECM) 분해에 관여하여 다양한 염증성 피부질환을 유도하는 유전자인 matrix metalloproteinase (MMPs)를 조절하는 효과를 RT-PCR을 통해 확인하였다. Ab4-7은 강력한 항염증 및 항산화 효과를 가지고 있으며, 항염증 및 항산화 효과를 통한 MMPs 관련 유전인자 조절을 통해 다양한 염증성 피부질환 치료제의 기능성 재료로 활용될 수 있다고 사료된다. Abalone, a marine organism inhabiting the west coast of Korea, has antioxidant and anti-inflammatory effects, and is a resource with potential to be used in various industries such as antibiotic development and cosmetic raw materials. In this study, we chose abalone among various marine lives on the west coast. Antibacterial peptide (AMP) was separated from abalone and its derivative Ab4-7 was identified and its physiological activity was studied. The treatment of Ab4-7 in inflammatory RAW 264.7 to check the anti-inflammatory efficacy nhibited inflammatory cytokines, TLR4, TNF-α, IL-1β, COX-2, and iNOS and increased mRNA manifestation of HO-1, genes related to antioxidants. Based on the strong antioxidant and anti-inflammatory effects of Ab4-7, the effects of Ab4-7 in the inflammatory RAW 264.7 cells were identified through RT-PCR, which regulates the gene Matrix Metalloproteinase (MMPs) that induces a variety of inflammatory skin diseases by engaging in the decomposition of the extrocellular matrix metalloproteinase (ECM). Taken together, it is concluded that Ab4-7 has a powerful anti-inflammatory and antioxidant effect and can be used as a functional material for various inflammatory skin disease treatments by controlling the genes associated with matrix metalloproteinase (MMPs).

Omeprazole 투여시 위산분비 억제능에 대한 CYP2C19 의 영향

박수헌(Soo Heon Park),김종원(Jong Won Kim),이수연(Soo Youn Lee),최명규(Myung Gyu Choi),김재광(Jae Kwang Kim),정인식(In Sik Chung),정규원(Gyu Won Chung),선희식(Hee Sik Sun),박두호(Doo Ho Park) 대한소화기학회 2001 대한소화기학회지 Vol.38 No.6

Background/Aims: CYP2C19 has an important role in the catabolism of several proton pump inhibitors. However, the relative contribution of CYP2C19-mediated metabolism varies among the different proton pump inhibitors. We investigate to determine the effect of CYP2C19 genotype status on intragastric pH during dosing with omeprazole. Methods: The subjects were 16 healthy volunteers. Their CYP2C19 genotype status was determined by a polymerase chain reaction-restriction fragment length polymorphism method. Twenty-four-hour monitoring of intragastric acidity were performed on the day without medication and day 4 after omeprazole administration. Results: A single dose of omeprazole significantly decreased 24 hour intragastric acidity (1.7±0.3 vs. 5.1±0.4). Subjects were divided into three groups on the basis of their CYP2C19 genotype status: homozygous extensive metabolizers (Ho-EMs, n=5), heterozygous extensive metabolizers (Ht-EMs, n=6), and poor metabolizers (PMs, n=5). Median 24 hour intragastric pH in the Ho-EM group was 3.1 compared with 5.5 in Ht-EM group and 5.9 in PM group(P<0.05). The median pH during omeprazole administration was influenced by CYP2C19 genotype. On the other hand, the Helicobacter pylori infection did not influence the median intragastric pH during omeprazole administration (p= NS). Conclusions: The effects of omeprazole on intragastric acidity is influenced by the CYP2C19 polymorphism. (Korean J Gastroenterol 2001;38:399-404)

Mycophenolic Acid에 의해 유도된 Jurkat 세포주 세포자멸사에서 Heme Oxygenase-1의 발현이 미치는 영향

이호균(Ho Kyun Lee),최수진나(Soo Jin Na Choi) 대한외과학회 2010 Annals of Surgical Treatment and Research(ASRT) Vol.78 No.6

Purpose: This study demonstrates that pharmacologic induction of heme oygenase-1 (HO-1) along with catalytic activation significantly modulated apoptosis of Jurkat cells induced by mycophenolic acid (MPA). Methods: Cells were cultured with the presence or absence of MPA. Flow cytometric analysis was performed after propidium iodide staining. Western blotting of HO-1, Bcl, and Bax was also performed. Cells were stained 4’-6-Diamidino-2-phenylindole (DAPI) and measured by flow cytometry in the absence or presence of CoPPIX. Results: Treatment of MPA decreased cell viability in a dose- and time-dependent manner. MPA-induced cell death was confirmed as apoptosis characterized by sub G0/G1 phase arrest. Expression of HO-1 assumes a pattern of decline after rising at the initial phase. CoPPIX, HO-1 inducer, significantly inhibited the cisplatin-induced apoptosis. Treatment of MPA resulted in reactive oxygen species (ROS) generation in Jurkat cells. CoPPIX attenuated ROS production in MPA-treated cells. Conclusion: This result suggests that the protective mechanism of HO-1 on MPA-induced cytotoxicity is associated with direct inhibition of ROS generation and mitochondrial permeability transition.

최근 10년간 원광의대병원에서 시행한 소아 심장혈관 수술의 임상적 고찰

윤향석,정수미,최두영,오광수,오연균,김종덕,양현웅,이삼윤,김형곤,최종범,최순호,노병석 圓光大學校 醫科學硏究所 1995 圓光醫科學 Vol.11 No.2

We reviewed 10 years experiences of the clinical aspects and early postoperative results in 544 pediatric patients(age less than 16 years old). Among them. 529 cases had the congenital heart diseases, and 15 had the acquired diseases. Open heart surgery was performed in 413 patients. 115 cases were treated with non-open heart surgery. 16 with interventional catheterization. Annual increase of the cardiac patients was not significant in recent 10 years, except slight increase in 1994. The mean age of the study patients had been evidently changed to younger year by year. Total mortality rate of the open heart surgery was 6.4%. The cyanotic congenital heart diseases were high in early postoperative mortality by 25.7%, whereas 4% in acyanotic group. The age group less than one month was most highest in surgical mortality(66.7%). There were no deaths in patients with patent ductus arteriosus(103 cases), atrial septal defect(83 cases) or pulmonary stenosis(17 cases). Among 220 patients with ventricular septal defects(VSD). 10(4.5%) were died early postoperatively. In cyanotic group, the patients with pulmonary atresia with ventricular septal defects(PAVSD), transposition of the great arteries(TGA), interrupted aortic arch(IAA), complex cardiac anomalies with isomerism seemed to be most susceptible to an early death.

말초동맥질환에 있어서 혈장 호모시스테인 농도의 의미

최동현,이상목,고석환,홍성화,오수명,윤충,박호철 대한혈관외과학회 2004 Vascular Specialist International Vol.20 No.1

쌍생아에서 발생한 급성 골수성백혈병 -증례보고-

이혜수,최호열,박숙자 대한병리학회 1982 Journal of Pathology and Translational Medicine Vol.16 No.4

Hypophosphatasia 환아의 치료 증례

최병제,최형준,이제호,김기덕,박수정 大韓小兒齒科學會 1998 大韓小兒齒科學會誌 Vol.25 No.3

1. Hypophosphatasia 는 골조직 및 치아조직의 비정상적인 석회화를 나타내는 대사장애로, 특징적구강내 소견 인 우치의 조기탈락 양상으로 치과에서 조기진단이 가능하다. 2. 본 증례에서 상악궁 확장을 동반한 의치 제작으로 심미적, 기능적으로 양호한 결과를 얻었으며, 영구치열기 까지 장기적 관찰 및 치료가 필요할 것으로 사료된다. hypophosphatasia is a rare metabolic disorder which manifests characteristics such as abnormal mineralization of bone and dental tissues, diminished serum and tissue alkline phosphatase, and increased urinary secretion of PEA. It ingerited as an autosomal recessive or dominant trait and occurs in all races. In general, hypophosphatasia can be classified in 4 subtypes which are the perinatal, infantile, childhood, adult type depending upon the age at presentation and severity. In young children with Hypophosphatasia the long bones show irregular defects, and the skull showes poor calcification. In older children with premature closure of the skull sutures there may ve multiple lucent area called gyral or convolutional markings, described as resimbling beaten copper, presumably resulting from increased intracranial pressure,Examination of the jaws reveals a generalized lucency of the maxilla and mandible, the cortical bone and lamina dura are thin, and the alveolar bone may be deficient. Clinical features of Hypophosphatasia imclude premature loss of deciduous teeth, especially incisors, hypoplasia of aplasia of root cementum, enamel hypoplasia, irregular calcification of dentin, large pulp chamber, and resorption of marginal alveolar bone and roots. Our report involves a patient with a chief complaint of early loss of both Mx. and Mn. deciduous ncisors. after conducting a through clinical and radiographic examination this patient was referred to pediatrics under the suspicion of hypophosphatasia, the diagnosis proved to be correct and successful results were accomplished through a denture made to improve esthetics and function.

Starter 및 멸치액젓 첨가가 김치양념 및 겉절이 김치의 품질에 미치는 영향

최택권,박소희,유진현,임호수,조재선,황성연 한국식생활문화학회 2003 韓國食生活文化學會誌 Vol.18 No.2

양념에 Leu. mesenteroides, Lac plantarum의 젖산균과 멸치액젓 첨가가 김치 양념의 대장균군 제어, 속성촉진여부 및 관능적 특성에 미치는 영향을 조사하였다. Leu. mesenteroides과 젓갈을 첨가한 경우 초기 숙성이 촉진되나 후기 산패는 완만하였으며 Lac. plantarum의 첨가시에는 초기 숙성에는 큰 차이가 없고 후기 산패가 현저하게 진행되었다. 대장균군은 산도 0.80% 이상에서 사멸되었는데 leu. mesenteroides의 경우가 숙성이 촉진되어 보다 신속히 사멸시켰다. 총균수와 젖산균수는 초기에 starter 첨가구는 10^6CFU/mL 정도인데 반해서 starter를 첨가하지 않은 않은 처리구에서 총균수는 10^6CFU/mL , 젖산균수가 10^4CFU/mL 이었고 숙성 후에는 첨가균이 높은 수준을 유지하였다. 하지만 대체적으로 스타터의 첨가가 숙성 및 대장균에 크게 영향을 주지 못하는 경향으로 동일하게 나왔다. 관능적 특성에서는 Leu. mesenteroides 첨가구가 Lac. plantarum의 경우보다 우수하였다. 한편, 시판 겉절이 김치는 산도가 0.09~0.18%, ph 5.46~5.89, 총균수 2.2×10^6~3.1×10^7CFU/mL, 젖산균수는 2.1×10^4~6.6×10^5CFU/mL, 대장균수는 1.8×10^4~7.1×10^5CFU/mL, 염분 1.89%~2.51%으로 스타터 첨가 겉절이에 비해 ph와 염도를 제외한 품질 특성에서 전반적으로 낮은 값을 나타냈다. This study was performed in order to investigate the effect of Leuconostoc mesenteroides, Lactobacillus plantarum and salt fermented anchovy extracts on Kimchi sauce. The sauce was fermented more rapidly by addition of Leu. mesenteroids or salt fermented anchovy extracts on the early fermentation stage than the control, but it was fermented slowly on the late fermentation stage. When L. plantarum was added to the Kimchi on the early fermentation stage, the acidity of Kimchi didn't show a significant difference from the control, but acidity was remarkably increased on the late stage. Coliform group was disappeared when acidity of sauce was higher than 0.8% during fermentation. It was controlled by Leu. mesenteroides but not by L. plantarum. Total count and lactic acid bacterial count of the sauces with starter were 6.30×10^6~1.0×10^7 CFU/mL and 1.04~2.04×10^6 CFU/mL, respectively, but those of the control sauce were 10^6 CFU/mL and 10^4 CFU/mL, respectively. Those count of the sauce with starter were higher than those of the control sauce on the later stage of fermentation. Organoleptic quality of the sauce with Leu. mesenteroides was superior to that with L. plantarum.