• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.135-143
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• 2018

Tumor necrosis $factor-{\alpha}$ ($TNF{\alpha}$) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which $TNF{\alpha}$-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS ($10{\mu}g/ml$) in the presence or absence of a type 1 TACE inhibitor ($1{\mu}M$) or type 2 TACE inhibitor ($10{\mu}M$). LPS treatment induced increased serum creatinine, $TNF{\alpha}$, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore, inhibitors of TACE are potential therapeutic agents for kidney injury.

• Mycobiology
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• 제39권2호
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• pp.137-139
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• 2011

A Vitis hybrid-Vitis coignetiae red wine was vinified by fermentation of a mixture of a Vitis hybrid.Vitis coignetiae must with Saccharomyces cerevisiae KCTC 7904 at $25^{\circ}C$ for 10 days. The Vitis hybrid-Vitis coignetiae red wine showed high antihypertensive angiotensin I-converting enzyme (ACE) inhibitory activity (67.8%) and antioxidant activity (76.7%). The antihypertensive ACE inhibitor in the Vitis hybrid-Vitis coignetiae red wine was partially purified by solid phase extraction chromatography, and its ACE inhibitory activity yielded an $IC_{50}$ of 1.8 mg/mL. Six kinds of oligopeptides, including five new kinds, were contained in the partially purified ACE inhibitor fraction from the red wine after 10 days of fermentation. Antioxidant activity decreased significantly from 76.7% to 40.5% when the post-fermentation period was prolonged to 30 days.

• Preventive Nutrition and Food Science
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• 제5권2호
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• pp.75-80
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• 2000

To separate ACE inhibitors from edible plants, spices, and herbs, 285 extracts of 95 sources were screened for ACE inhibitory activity. The extract of Sinapis alba L. had the most potent ACE inhibitory activity. Mustard seeds were crushed homogeneously and extracted with hexane and water successively. Lyophilized water extract was fractionated with $H_2O$:butanol(1:1). The ACE inhibitor was purified from butanol fraction by methanol precipi-tation, gel filtration, HPLC, and FPLC with Superdex peptide HQ 10/30 column. The active fraction has been purified to homogeneity, which was proven by gel filtration using FPLC system. The yield was 0.02%. The com-pound has a molecular weight of about 640. The compound competitively inhibited ACE activity and the $IC_{50}$ value was 79$\mu\textrm{g}$/ml. The purified compound showed uterus contraction activity in isolated rat uterus.

• Food Science and Biotechnology
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• 제17권4호
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• pp.873-877
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• 2008

Native soy protein isolate (SPI) was hydrolyzed with 4 different proteolytic enzymes, including bromelain, papain, Neutrase, and Flavourzyme. SPI hydrolysates with the degree of hydrolysis (DH) in range of 6 to 15% were prepared by each enzyme. The angiotensin 1 converting enzyme (ACE) inhibitory and the antioxidant activities of the SPI hydrolysates, such as superoxide dismutase-like activity and inhibition of the linoleic acid autoxidation, were evaluated. Overall, as the DH increased, all evaluated bioactivities of the SPI hydrolysates significantly increased. The significantly highest ACE inhibitory and antioxidant activities were found in hydrolysates made with papain and bromelain, respectively. SPI hydrolysates by Flavourzyme showed the significantly lowest activity in all tested bioactivities. The results suggested that ACE inhibitory and antioxidant activities of SPI hydrolysates were determined by the DH and by the enzyme used.

• 한국수산과학회지
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• 제34권2호
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• pp.164-172
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• 2001

본 연구는 김의 Maxazyme NNP 가수분해물로부터 여러 단계의 column chromatography 및 HPLC를 통해 ACE 저해 peptide를 분리, 정제하여 이의 분자량과 amino acid sequence를 분석하였다. ACE 저해 효과가 큰 저분자 peptide의 함량이 많은 가수분해물을 얻기 위한 최적의 단백질 가수분해 효소를 선정하기 위하여 시험한 결과, Maxazyme NNP에 의한 가수분해물의 ACE 저해효과가 $37.2\%$로 가장 높게 나타났다 김의 효소 가수분해물로부터ACE 저해 peptide만을 효율적으로 분리하기 위한 추출 조건 시험에서, 색소 제거를 위해서는 diethylether 처리가, 다당류 및 고분자 단백질 제거를 위해서는 $70\%$ ethanol 처리가 각각 선정되었다. 김 가수분해물로부터 ACE 저해 peptide를 분리, 정제하기 위한 첫 단계로 ultrafiltration을 한 결과, 분자량 3,000 이하 분획물의 ACE 저해 효과가 $69.4\%$로 가장 높았으며, 이 분획물을 gel filtration chromatography (Sephadex G-25) , reverse-phase HPLC (ODS & Vydac C-18) 및 gel permeation chromatography (Superdex Peptide HR)와 같은 단계별 column chromatography를 행하여 최종적으로 단일 peptide peak들을 분리하였다. 이들 단일 peptide peak들의 분자량을 Electrospray-Mass Spectrometer로 측정한 결과, 각각 413.48 (S1O2V2V1P),346.86 (S1O2V2V2P) 그리고 320.32 (S2O6V3V1P) dalton이었으며, 이들 peptide의 amino acid sequence는 N-말단으로부터 아미노산 잔기를 분석한 결과, 각각 Val-Gln-Gly-Asn, Thr-Glu-Thr 및 Phe-Arg으로 확인되었다.

• 생명과학회지
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• 제28권2호
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• pp.187-194
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• 2018

표고버섯으로부터 유래한 eritadenine (EA)은 혈중 low density lipoprotein (LDL), triglyceride (TG), phospholipid를 감소시키는 물질이다. 최근 저희 연구팀은 in vitro 연구에서 EA가 angiotensin converting enzyme (ACE)의 활성을 저해함을 밝혔다. 본 연구에서는 EA와 EA 함유한 표고버섯균사체 고체배양 효소추출물(EA-LEMCEE)이 본태성 고혈압 쥐 SHR의 혈압을 낮추었음을 보고한다. EA 및 EA-LEMSCEE는 인체 탯줄 혈관내피세포 EA.hy926 세포의 ACE 활성을 억제하였다. EA-LEMSCEE는 SHR의 수축기 및 이완기 혈압을 Control 처리구에 비해 유의성 있게 낮추어 처리 5주에는 Positive control인 captopril (CP) 처리와 비슷한 혈압감소 효과를 나타내었다. EA-LEMCE는 LEMSCEE에 비해 수축기 및 이완기 혈압을 감소시켰지만 유의성은 없었다. EA- LEMSCEE는 renin과 ACE 활성을 Control 처리에 비해 유의성 있게 억제하였고, angiotensin II (Ang II) 함량을 감소시켜, 처리 5주 후에 이러한 CP의 효과와 유사하였다. 또한 EA-LEMCEE는 LEMCEE에 비해 유의성 있게 renin 및 ACE 활성을 억제하였고 및 Ang II 함량을 감소시켰다. 이와 같은 결과는 EA 및 EA-LEMCEE는 본태성 고혈압 SHR의 renin과 ACE 활성을 억제하여 혈압을 낮추었고, EA 및 EA-LEMSCEE는 인체 고혈압을 낮출 수 있음을 의미한다.

• 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.

• 동의생리병리학회지
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• 제18권5호
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• pp.1505-1511
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• 2004

Inhibition of angiotensin converting enzyme (ACE) activity is one of the common antihypertensive methods functioned by drugs such as captopril, lisinopril and enalapril to serve as inhibitors of ACE. This study was designed to compare the effects of enalapril, an angiotensin-converting enzyme inhibitor and GLM002, an oriental medicine, on tail systolic pressure, aorta and plasma properties in spontaneously hypertensive rats (SHR) after 4 weeks of treatment. During the treatment, blood pressure was depressed to normal in GLM002 and enalapril groups. The treatments of enalapril and GLM002 were discontinued in 4 weeks. One week after the treatment stop, systolic blood pressure was smoothly increased in both groups; the increment of blood pressure was slightly greater in GLM002-SHR, but the increment of plasma ACE activity was proportionately similar in each group. In the aspects of the triglyceride, HDL and total cholesterol level, those levels were slightly different among each group. We also conducted clinical dosage of GLM002 to the patients who have mild and severe hypertension for approximately 7 weeks. Clinical treatments also showed remarkable efficiencies on blood pressure (systolic blood pressure, diastolic blood pressure), complete blood count (CBC) routine, differ count (NEUTRO, LYM, MONO, EOS and BASO) and R-chemistry. We conclude that GLM002, like already proven enalapril, plays a role as an angiotensin-converting enzyme inhibitor, and can be suggested as a drug candidate for curing hypertension.

• 한국식품영양학회지
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• 제18권1호
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• pp.11-18
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• 2005

Angiotensin Ⅰ converting enzyme(ACE) inhibitory activities of laver(Porphyra tenera) protein hydrolysates were investigated by enzymes used for hydrolysis, molecular fractions and drying methods. For the enzymatic hydrolysis, crude laver protein, separated by filtration of water extract of dried laver extracted with 20 times(w/v) water for 3 hours at boiling temperature, were hydrolyzed with three commercial protease, Pepsin, alcalase and maxazyme NNP at optimal conditions. The yield of hydrolysis and ACE inhibitory activities of which were high in order of pepsin, alcalase and maxazyme NNP. ACE inhibitory activities of laver hydrolysates by molecular levels were high in order of 3 kDa > 10 kDa > 3∼10 kDa, and the IC/sub 50/ ACE inhibitory activities by molecular lebels were 4 mg/mL(3 kDa), 5 mg/mL(total hydrolysate), and 20 mg/mL(10 kDa), respectively. The storage stability of dried laver hydrolysates at 20℃ were strongly affected by drying methods, hot air dried of which were much stabler than freeze-dried one.

• Preventive Nutrition and Food Science
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• 제3권4호
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• pp.379-381
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• 1998

An angiotensin converting enzyme (ACE) inhibitor was isolated and partially purified from bovine blood plasma. Bovine blood plasma was obtained after removing blood cells by centrifugation, followed by the addition of anticoagulant to whole bovine blood. To precipitate plasma proteins, bovine blood plasma was treated with 4% trichloroacetic acid (TCA) as a final concentration .An ACE inhibitor was isolated from TCA supernatnat, using ultrafiltration, gel permeation chormatography, and reverse-phase high pressure liquid chromatogrpahy. The ACE inhibitor purified from TCA supernatant had IC50 values of 9.4$\mu$M.