• 동의생리병리학회지
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• 제16권4호
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• pp.724-728
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• 2002

Angiotensin-converting enzyme (ACE) gene polymorphism, which consists of presence (insertion, I) or absence (deletion, D) of a 250-bp fragment, is associated with ischemic heart disease, renovascular disease, systemic lupus erythematosus. Subjects with the DD genotype have higher levels of circulating ACE than subjects with the II genotype and show an increased tendency towards vascular wall thickness and contribute to the development of vascular disease. But the association between I/D polymorphism of the ACE gene and cerebrovascular disease is still controversial. The aim of this study was to determine whether the DNA polymorphism of the ACE are associated with cerebrovascular disease in Korean population. The study group comprised 377 Korean patients admitted to Kyunghee Oriental Medical Center in the year of 2000 for the treatment of brain infarction or brain hemorrhage. Magnetic resonance imaging(MRI) was performed for each patient to determine the stroke phenotype, infarction or hemorrhage. The 183 subjects without evidence of brain infarction or brain hemorrhage were selected from the some ethnical population(control group). Venous blood samples were drawn from each subject for the extraction of DNA. Genotypes of ACE were determined by polymerase chain reaction amplification of the genomic DNA. Case and control genotype frequencies were compared by chi-square testing. Both the patients and the controls were classified respectively into 4 groups: age less than forty years, age forty one to fifty, age fifty one to sixty, age greater than sixty years. There were no significant differences in the distributions of ACE genotypes among the patients with infarction, with hemorrhage and controls (Infarction: D/D 15.8%, I/D 46.7%, I/I 37.5%, Hemorrhage: D/D 15.1%, I/D 46.5%, I/I 38.4%, Control: D/D 18.6%, I/D 50.3%, I/I 31.2%). There was a significant difference in the distribution of ACE genotypes between the age greater than sixty year subgroup of patient with brain hemorrhage and the control (Hemorrhage: D/D 0%, I/D 55.6%, I/I 44.4%, Control: D/D 13.0%, I/D 63.0%, I/I 23.9%; Pearson Chi-Square value 5.956, P<0.05). Furthermore, the frequency of the ACE D/D type declined with increasing age both in the patient and control group (Patient group: age < 50 D/D 21.5%, age > 50 D/D 14.42%; Control group: age < 50 D/D 21.0%, age > 50 D/D 14.2%). In conclusion there is no clear association between ACE polymorphism and cerebrovascular disease in Korean population. Although, there was a tendency for the frequency of the ACE D/D type declined with increasing age in both patients and controls.

• Advances in Traditional Medicine
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• 제4권2호
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• pp.104-111
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• 2004

Sasang Constitutional Medicine is a major branch of Korean Traditional Oriental Medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, we examined interrelationship among cerebral infarction (CI), apolipoprotein E (apoE) gene polymorphism, and Sasang constitutional classification. ApoE is a key protein modulating the highly atherogenic apoB containing lipoproteins and is a candidate gene for the development of coronary artery disease (CAD). The ${\varepsilon}2\;and/or\;{\varepsilon}4$ alleles were the first to be implicated in premature CAD, which resulted in this polymorphism being extensively studied. We investigated the association between apoE genotype and CI by case-control study in a Korean population. We also classified CI patients and control group into groups according to Sasang Constitutional Medicine. 196 CI patients and 379 controls without CI were examined. ApoE genotype was determined by 8% polyacrylamide gel separation after DNA amplification. A significant difference in the apoE genotype distribution was observed in the CI patients compared with that in controls ($X^{2}$=14.920, df=4, P=0.005). Also, the frequency of Taeumin constitution in patients with CI was significantly higher than that in controls (58.0% vs. 36.9%; P<0.001). However, the Taeumin constitution did not enhance the relative risk for CI in the subjects with apoE ${\varepsilon}2\;and/or\;{\varepsilon}4$ alleles. No differences in the apoE genotypes frequencies were observed in the Taeumin compared with that in the other constitutions. In addition, we investigated whether the DD genotype of angiotensin converting enzyme (ACE) gene, a candidate gene for CI, was associated with CI, Taeumin constitution, and apoE polymorphism. As a result, the frequency of Taeumin constitution was significantly higher in CI patients with both apoE ${\varepsilon}3/{\varepsilon}4$ and ACE ID/DD genotypes than in the remaining Sasang constitutions (14.5% vs. 8.3% and 0%) ($X^{2}$=13.521, df=6, P=0.035). In summary, we concluded that the apoE polymorphism is a major risk factor for CI in Koreans and the ACE ID/DD genotype enhanced the relative risk for CI in the subjects with apoE ${\varepsilon}3/{\varepsilon}4$ genotype and Taeumin constitution.

• Journal of Microbiology and Biotechnology
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• 제12권1호
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• pp.59-64
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• 2002

An angiotensin I-converting enzyme (EC 3.4.15.1) (ACE), which can convert inactive angiotensin I into angiotensin II, a vasoconstrictor, is one of the key enzymes in controlling hypertension. It is suggested that the inhibition of ACE prevents hypertension, and many inhibitory peptides have already been reported. In the current study, oligonucleotides encoding ACE inhibitory peptides (IY, VKY) were chemically synthesized and designed to be multimerised due to isoschizomer sites (BamHI, BglII). The cloned gene named AP3 was multimerised up to 6 times in pBluescript and expressed in BL2l containing pGEX-KG. The fusion protein (GST-AP3) was easily purified with a high recovery by an affinity resin, yielding 38 mg of synthetic AP3 from a 1-1 culture. The digestion of AP3 by chymotrypsin exhibited an $IC_50$ value of $18.53{\mu}M$. In conclusion, the present experiment indicated that AP3 could be used as a dietary antihypertensive drug, since the potent ACE inhibitory activity of AP3 could be activated by chymotrypsin in human intestine.

• BMB Reports
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• 제37권5호
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• pp.552-555
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• 2004

Several studies have demonstrated the importance of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms in the pathogenesis of hypertension. This study sought to determine the association between the ACE I/D polymorphism and essential hypertension in young Pakistanis. The frequency of the ACE I/D polymorphism was established by a comparative cross-sectional survey of Pakistani patients suffering from essential hypertension and ethnically matched normotensive controls. Samples were collected from tertiary care hospitals in northern Pakistan. Hypertensive individuals were defined as those with a systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg on three separate occasions, or those currently receiving one, or more, anti-hypertensive agents. DNA samples obtained from hypertensive (n=211) and normotensive (n=108) individuals were typed by PCR. The frequency of the ACE I/I genotype was significantly higher in hypertensive patients, aged 20-40 years, than in normotensive controls of the same age group ($\chi^2$ = 4.0, P = 0.041). Whereas no overall significant differences were observed between the I/I, I/D and D/D ACE genotypes (One way ANOVA, F=0.672; P=0.413). The association between the ACE I/I genotype and essential hypertension in individuals aged $\leq$ 40 years suggests that ACE has a role in early onset essential hypertension in Pakistan.

• 생명과학회지
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• 제21권10호
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• pp.1428-1433
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• 2011

본 연구에서는 ACE 저해능 및 항산화능이 있는 식물성 젖산균을 다양한 식물체로부터 분리한 후, 그 특성을 조사하였다. 김치, 부추, 포도 및 동동주에서 K-1, K-21, L-5, G-3 및 D-3 균주가 분리되었으며, 16S rRNA gene 염기서열 분석을 통하여 이들은 각각 Pediococcus pentosaceus, Lactobacillus plantarum, Weissella cibaria, L. plantarum 및 L. brevis로 동정되었다. 분리균주들은 MRS broth에서 44.3-71.9%의 ACE 저해능을 나타내었으며, 특히 G-3, L-5, K-1 균주는 skim milk가 함유된 MRS broth에서 59.0-8-98.6%의 높은 ACE 저해능을 나타내었다. 분리 균주는 42.5-82.7%의 DPPH radical 소거능을 나타내었으며, G-3 및 K-1 균주는 pH 2.5의 인공위액에서 42.2-88.1%의 높은 생존율을 나타내었다. 분리균주는 0.3% oxgall에서 24시간 배양시 55.4-112.8%의 내성을 나타내었다. 또한 분리균주는 유기산 생성에 따른 pH 감소 효과로 인하여 Pseudomonas aeruginosa를 포함한 일부 병원성 세균의 생육을 억제할 수 있었다.

• 미생물학회지
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• 제46권2호
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• pp.134-139
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• 2010

전 세계 인구의 1/3을 감염시키고 있는 결핵균은 21세기에도 인류를 위협하는 병원균이다. 결핵균에 대항하는 Th1 면역 반응은 결핵균의 세포 내 성장을 제어하는 것으로 알려져 있으나, 이는 결핵균 감염을 자연 치유하는 수준에는 미치지 못한다. 본 연구에서는 C57BL/6 마우스에 병원성 결핵균인 H37Rv를 감염시켰을 때 숙주의 면역 반응에 대항하여 결핵균이 자신의 유전자 발현을 변화시킨다는 사실을 규명하기 위하여, 결핵균 유전자 중 16S rRNA, acr, fbpA, aceA, ahpC 등의 발현을 real-time RT-PCR을 이용하여 연구하였다. 16S rRNA의 copy number는 감염 후 30일까지 급격하게 증가하였는데 이는 CFU 측정 결과와 일치하고 있다. 결핵균 유전자 중 주된 항원으로 작용하는 유전자인 fbpA의 copy number를 CFU로 나눈 값으로 표현한 발현 양상은 감염 후 10일까지 증가하다가 감소되었다. Heat shock protein인 ${\alpha}$-crystallin을 coding하는 acr은 감염 후 지속적으로 높아졌으나, 산화적 스트레스 환경에서 발현되는 효소들인 ahpC와 aceA의 발현은 감염 후 20일 동안 높아졌다가 30일에는 약간 감소하였으나 비교적 높은 수준을 유지하였다. 이상의 결과는 결핵균이 숙주의 면역 반응이 개시되면 결핵균의 주된 항원 중 하나인 Ag85A를 코딩하는 유전자인 fbpA의 발현 수준을 낮춰 숙주의 Th1 먼역 반응이 낮아지도록 유도한다는 증거로 볼 수 있으며, 면역 반응이 활발해 짐에 따라 큰포식세포 내에서 산화적 스트레스로부터 균을 보호하기 위하여 ahpC와 aceA의 발현이 높아진 것으로 해석된다. 따라서 본 연구는 결핵균이 유전자 발현을 숙주의 면역 반응에 대항하여 스스로 변화시켜 적대적인 숙주 세포 내에서 살아 남을 수 있는 생존 전략을 구사한다는 가능성을 제시한다.

• Journal of Microbiology and Biotechnology
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• 제6권5호
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• pp.315-320
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• 1996

The role of glyoxylate bypass in a lysine-producing Corynebacterium lactofermentum strain was analyzed. Unlike the wild type, the strain expressed enzymes of glyoxylate bypass during growth in the fermentation broth containing glucose as the carbon source. To evaluate the importance of glyoxylate bypass in the strain, we disrupted chromosomal aceA by using a cloned fragment of the gene. Site-specific disruption of aceA which codes for the isocitrate lyase, the first enzyme of the bypass, was confirmed by Southern blot analysis. The aceA mutant strain completely lost isocitrate lyase activity and ability to grow in a minimal medium containing acetate as the sole carbon source. The mutant strain was similar to its parental strain in growth characteristics and produced comparable amounts of lysine in shake flasks containing glucose as the carbon source. The amount of oxaloacetate accumulated in the fermentation medium was similar for both strains, suggesting that expression of glyoxylate bypass does not necessarily lead to the increase in intracellular oxaloacetate. These data clearly demonstrate that glyoxylate bypass does not function as one of the routes of carbon supply for lysine production in the strain. It appears that the leakiness of the glyoxylate bypass in the strain might be the result of a secondary mutation which arose during previous strain development by random mutagenesis.

• Journal of Microbiology and Biotechnology
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• 제12권2호
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• pp.336-339
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• 2002

A total of 100 Corynebacterial clones exerting a regulatory effect on the aceB promoter of Corynebacterium glutamicum were isolated by utilizing a reporter carrying the enteric lacZ gene fused to the promoter. The isolated clones were classified into 3 groups of A, B, and C, according to their color of colonies. Escherichia coli cells carrying clones in groups A and B showed a $90\%\;and\;50\%$ reduction in ${\beta}$-galactosidase activity, respectively. The introduction of group A clones into C. glutamicum also resulted in an almost complete reduction in the expression of the aceA and aceB genes, suggesting that the clones express repressor-like proteins for the genes. Although white colonies were formed on plates containing X-gal, E. coli cells carrying one of the clones in group C exhibited intact ${\beta}$-galactosidase activity. The result suggests that the clone may encode proteins that prevent the cells from accumulating the chromogenic compound, X-gal.

• 한국식품영양과학회지
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• 제44권7호
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• pp.1084-1089
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• 2015

고품질 감귤 가공품 개발을 위하여 감귤에 7종의 유산균을 각각 접종하여 10일간 배양하면서 0, 3, 5, 7, 10일째의 발효물의 생리활성을 분석하였다. 병원성 미생물에 대한 감귤 발효물의 항균 활성을 측정한 결과 김치에서 분리한 유산균인 CL-1과 CL-2의 발효물이 발효기간이 길어질수록 강한 항균 활성이 나타났다. 또한 각 감귤 발효물의 항고혈압 활성을 ACE 저해능으로 분석하였을 때 CL-1과 CL-2의 발효물이 발효기간이 길수록 높은 활성을 나타내었다. CL-1과 CL-2 균주를 16S rRNA gene의 구조로 분자계통학적 유연관계를 파악한 결과 각각 Pediococcus acidilactici 및 Lactobacillus sakei와 99% 이상의 상동성을 가지는 것을 확인할 수 있었다. 이상의 결과는 감귤을 P. acidilactici와 Lac. sakei로 발효하여 항균력과 항고혈압능이 증진된 가공품의 제조에 활용이 가능함을 시사한다.

• 응용통계연구
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• 제18권2호
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• pp.297-310
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• 2005

본 연구에서는 강화연구(서일, 2004)를 통해 수집된 277명의 환자-대조군 자료와 40개의 가계 자료를 이용하여 ACE(angiotensin-I converting enzyme) 유전자 내에 있는 4개의 단일염기다형성(single nucleotide polymorphism; SNP)으로 이루어진 일배체형(haplotype)과 고혈압의 관련성을 알아보고자 한다. 이를 위해 일배체형에 기초한 환자-대조군의 우도비 검정과 가계 자료의 TDT(transmission/disequilibrium test) 연구를 수행하고자 한다. 또한 이 일배체형을 동정(identification)할 수 있는 tag-SNPs에 기초하여 동일한 연구를 하고자 하며, Seltman 등(2003)이 제안한 분기도(cladogram) 분석 방법을 써서 일배체형의 진화 과정에서 가깝게 위치하고 질병 발생 위험이 비슷한 클레이드(clade)를 찾아내고 이 클레이드와 고혈압의 연관성을 살펴보고자 한다.