Properties and Human Origin of Two Angiotensin-I-Converting Enzyme Inhibitory Peptides Isolated from a Tryptic Hydrolysate of Human Serum Albumin.

Nakagomi, Kazuya; Ebisu, Hidetoshi; Sadakane, Yutaka; Fujii, Nobutaka; Akizawa, Toshifumi; Tanimura, Takenori

doi:10.1248/bpb.23.879

Cited by 21 publications

(20 citation statements)

References 2 publications

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“…The majority of peptides were competitive inhibitors, and the remainder were non-competitive inhibitors. For instance, Nakagomi et al [19] obtained 2 types of ACE-inhibitory peptide from the separation of a trypsin enzymolysis solution of human plasma. These peptides were able to inhibit the activity of ACE and diminish the production of angiotensin II, and thus prevent elevations in blood pressure.…”

Section: Antihypertensive Effect and Half-life Of Ace-inhibitory Peptmentioning

confidence: 99%

Long-Term Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitory Peptide LAP

Luo¹,

Shen²,

Liu³

et al. 2011

Kidney Blood Press Res

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Objective: To study the antihypertensive effects of the angiotensin-converting enzyme (ACE)-inhibitory peptide LAP on blood pressure in spontaneously hypertensive rats (SHRs). Methods: A cohort of 12-week-old SHRs was randomly divided into 2 distinct groups, and ACE-inhibitory peptide LAP (experimental group) or physiological saline (controls) were administered. Caudal arterial blood pressure was then measured at specific time points (0, 4, 8 and 12 weeks). Results: Systolic blood pressure of the SHRs showed a significant decrease after intraperitoneal injection with the ACE-inhibitory peptide LAP. Moreover, this depressurization effect lasted for over 1 month. Conclusion: Systolic blood pressure of SHRs could effectively be depressed in the long term by antihypertensive activity mediated by the ACE-inhibitory peptide LAP.

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Section: Antihypertensive Effect and Half-life Of Ace-inhibitory Peptmentioning

confidence: 99%

Long-Term Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitory Peptide LAP

Luo¹,

Shen²,

Liu³

et al. 2011

Kidney Blood Press Res

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“…Four of the seven peptides, namely Val-Tyr, Ile-Tyr, P h e -T y r and Ile-Trp, show statistically significant antihypertensive effects. Furthermore, three of these four peptides, namely Ile-Tyr, P h e -T y r and Ile-Trp, apparently decrease blood pressure, even at 0.1 mg k g -1 It is known that small peptides such as di-or tripeptides are easily absorbed in the intestine (Nakagomi et al, 2000). Such peptides are resistant to gastrointestinal proteases.…”

Section: Blood Pressure Lowing Activitymentioning

confidence: 99%

Production of the blood pressure lowing peptides from brown alga (Undaria pinnatifida)

Sato

Oba

Hosokawa

et al. 2005

J Ocean Univ. China

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Brown alga ( Undaria pinnatifida ) was treated with alginate lyase and hydrolyzed using 17 kinds of proteases and the inhibitory activity of the hydrolysates for the angiotensin-I-converting enzyme (ACE) was measured. Four hydrolysates with potent ACE-inhibitory activity were administered singly and orally to spontaneously hypertensive rats (SHRs). The systolic blood pressure of SHRs decreases significantly after single oral administration of the brown alga hydrolysates by protease S 'Amano' (from Bacillus stearothermophilus) at the concentration of 10 (mg protein) (kg body weight) -1. In the 17 weeks of feeding experiment, 7-week-old SHRs were fed standard diet supplemented with the brown alga hydrolysates for 10 weeks. In SHRs fed 1.0 and 0.1% brown alga hydrolysates, elevating of systolic bloodpressure was significantly suppressed for 7 weeks. To elucidate the active components, the brown alga hydrolysates were fractionated by 1-butanol extraction and HPLC on a reverse-phase column. Seven kinds of ACE-inhibitory peptides were isolated and identified by amino acid composition analysis, sequence analysis, and LC-MS with the results Val-Tyr, Ile-Tyr, Ala-Trp, Phe-Tyr, Val-Trp, Ile-Trp, and Leu-Trp. Each peptide was determined to have an antihypertensive effect after a single oral administration in SHRs. The brown alga hydrolysates were also confirmed to decrease the blood pressure in humans.

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“…8) Several enzyme inhibitory peptides have also been isolated from enzymatic hydrolysates of proteins. [9][10][11][12][13][14] We previously isolated Acein-1 10) and Acein-2, 11) which are novel peptides that inhibit angiotensin I-converting enzyme (ACE). Acein-1 was isolated from a tryptic hydrolysate of human plasma with the amino acid sequence of Tyr-LeuTyr-Glu-Ile-Ala-Arg, which corresponds to f(138-144) of human serum albumin.…”

Section: 7)mentioning

confidence: 99%

“…Many bioactive peptides have been isolated from enzymatic hydrolysates of proteins. [9][10][11][12][13][14][26][27][28][29] However, only a few peptides have so far been isolated from enzymatic hydrolysates of human proteins. Other than casoxin D (YVPFPPF), which was isolated from a peptic hydrolysate of human casein as a bradykinin agonist, 27) Acein-1, Acein-2, Ala-Trp, and human albutensin A, all of which are ACE inhibitory peptides, are the only peptides that have been isolated to our knowledge.…”

Section: )mentioning

confidence: 99%

“…Other than casoxin D (YVPFPPF), which was isolated from a peptic hydrolysate of human casein as a bradykinin agonist, 27) Acein-1, Acein-2, Ala-Trp, and human albutensin A, all of which are ACE inhibitory peptides, are the only peptides that have been isolated to our knowledge. [10][11][12] Cabin-1, -2, -3, and -4 might be valuable because they are derived from enzymatic hydrolysates of human serum proteins, although the IC 50 values of these peptides were less than those of synthetic cathepsin B inhibitors such as E-64 (IC 50 3.4 nmol/l) and CA-074 (L-3-trans-(propylcarbamoyl)oxirane-2-carbonyl)-Lisoleucyl-L-proline (IC 50 2.2 nmol/l). 30,31) The present results suggest that Cabin-1, -2, -3, and -4 could be used as new leads for anti-cathepsin B drugs, although it is not yet known whether these peptides are released from serum proteins by endogenous thermolysin-like enzymes in the human body to act as internal cathepsin B inhibition.…”

Section: )mentioning

confidence: 99%

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Isolation of Novel Peptides, Cabin-1, -2, -3, and -4, That Inhibit Cathepsin B from a Thermolysin Digest of Human Plasma.

Nakagomi

Fujimura

Maeda

et al. 2002

Biological & Pharmaceutical Bulletin

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Lysosomal cysteine proteases are known to play important roles in intracellular protein degradation 1) and bone resorption.2) They have also been implicated in various pathological processes such as tumor invasion and metastasis, 3) cartilage degradation in arthritis, 4) and muscular dystrophy. 5) Among these lysosomal enzymes, cathepsin B (EC 3.4.22.1) represents a major component that exhibits both endopeptidase and exopeptidase activities. Cathepsin B has also been described as a strong candidate for a prorenin-processing enzyme. 6,7)Recently, cathepsin B inhibitory peptides derived from bcasein such as PFPGPI and GPFPI have been reported by Lee and Lee. 8) Several enzyme inhibitory peptides have also been isolated from enzymatic hydrolysates of proteins. [9][10][11][12][13][14] We previously isolated Acein-1 10) and Acein-2, 11) which are novel peptides that inhibit angiotensin I-converting enzyme (ACE). Acein-1 was isolated from a tryptic hydrolysate of human plasma with the amino acid sequence of Tyr-LeuTyr-Glu-Ile-Ala-Arg, which corresponds to f(138-144) of human serum albumin. Acein-2 (Leu-Ile-Tyr) was isolated from the same hydrolysate, which corresponds to f(518-520) of human a2-macroglobulin. These findings strongly suggest the possibility of isolating some novel cathepsin B inhibitory peptides from enzymatic hydrolysates of proteins.Almost all organisms, including animals, plants, and microorganisms, as well as a large number of synthetic compounds have been examined in the search for bioactive substances as starting materials for medicines.15-18) However, we believe that the human body might be the best resource for such bioactive peptides because such substances would be expected to be less toxic to humans. We have therefore been attempting to discover novel bioactive peptide sequences in human proteins.In this paper, we report the isolation of four novel peptides that inhibit cathepsin B, designated as Cabin-1, -2, -3, and -4, from a thermolysin (EC 3.4.24.4) digest of human plasma.To our knowledge, this is the first report on the isolation of cathepsin B inhibitory peptides from human protein. We also discuss their inhibitory mechanisms based on Lineweaver-Burk plot analysis. MATERIALS AND METHODSInhibitory Assay for Cathepsin B Inhibitory activity of cathepsin B was measured spectrofluorometrically using ZArg-Arg-MCA as the substrate as described by Barret and Kirschke 19) with a slight modification. Cathepsin B (from human placenta, Sigma, St. Louis, MO, U.S.A.) was dissolved in 50 mM sodium acetate buffer (pH 5.0) containing 0.2 M NaCl, 0.5 mM HgCl 2 , and 1 mM EDTA to a final concentration of 0.2 units/ml. A sample (100 ml) was mixed with 400 ml of 0.4 M sodium acetate buffer (pH 5.5) containing 4 mM EDTA, 200 ml of the enzyme solution, and 50 ml of 0.2 M L-cysteine in sodium acetate buffer (pH 5.5) and preincubated for 3 min at 37°C. A 250 ml aliquot of 40 mM Z-ArgArg-MCA (Peptide Institute, Osaka, Japan) in water was added and mixed to start the reaction at 37°C. After precisely 6 min, 1....

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Properties and Human Origin of Two Angiotensin-I-Converting Enzyme Inhibitory Peptides Isolated from a Tryptic Hydrolysate of Human Serum Albumin.

Cited by 21 publications

References 2 publications

Long-Term Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitory Peptide LAP

Long-Term Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitory Peptide LAP

Production of the blood pressure lowing peptides from brown alga (Undaria pinnatifida)

Isolation of Novel Peptides, Cabin-1, -2, -3, and -4, That Inhibit Cathepsin B from a Thermolysin Digest of Human Plasma.

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