Human placental leucine aminopeptidase (P-LAP) as a hypotensive agent

Mizutani, S; Okano, Kikumi; Hasegawa, Eiichi; Sakura, Harutake; Oya, Masakazu; Yamada, Mitsuhiro

doi:10.1007/bf01972292

Cited by 14 publications

(12 citation statements)

References 12 publications

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“…Systemic administration of APA in spontaneously hypertensive rats [124] or hypertensive rats infused with angiotensin II [125] reduced their blood pressure. Administration of amastatin, an APA inhibitor, raised blood pressure in normotensive rats [126].…”

Section: Resultsmentioning

confidence: 99%

Quantitative high-throughput profiling of snake venom gland transcriptomes and proteomes (Ovophis okinavensis and Protobothrops flavoviridis)

et al. 2013

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BackgroundAdvances in DNA sequencing and proteomics have facilitated quantitative comparisons of snake venom composition. Most studies have employed one approach or the other. Here, both Illumina cDNA sequencing and LC/MS were used to compare the transcriptomes and proteomes of two pit vipers, Protobothrops flavoviridis and Ovophis okinavensis, which differ greatly in their biology.ResultsSequencing of venom gland cDNA produced 104,830 transcripts. The Protobothrops transcriptome contained transcripts for 103 venom-related proteins, while the Ovophis transcriptome contained 95. In both, transcript abundances spanned six orders of magnitude. Mass spectrometry identified peptides from 100% of transcripts that occurred at higher than contaminant (e.g. human keratin) levels, including a number of proteins never before sequenced from snakes. These transcriptomes reveal fundamentally different envenomation strategies. Adult Protobothrops venom promotes hemorrhage, hypotension, incoagulable blood, and prey digestion, consistent with mammalian predation. Ovophis venom composition is less readily interpreted, owing to insufficient pharmacological data for venom serine and metalloproteases, which comprise more than 97.3% of Ovophis transcripts, but only 38.0% of Protobothrops transcripts. Ovophis venom apparently represents a hybrid strategy optimized for frogs and small mammals.ConclusionsThis study illustrates the power of cDNA sequencing combined with MS profiling. The former quantifies transcript composition, allowing detection of novel proteins, but cannot indicate which proteins are actually secreted, as does MS. We show, for the first time, that transcript and peptide abundances are correlated. This means that MS can be used for quantitative, non-invasive venom profiling, which will be beneficial for studies of endangered species.

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Section: Resultsmentioning

confidence: 99%

Quantitative high-throughput profiling of snake venom gland transcriptomes and proteomes (Ovophis okinavensis and Protobothrops flavoviridis)

et al. 2013

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“…APA, therefore, would be deeply involved in regulating BP through AngII metabolism. The findings that systemic administration of purified APA into spontaneous hypertensive rats (SHRs) 5) or AngII-infused hypertensive rats decreased their BP 6) and that APA inhibitor amastatin elevated BP in normotensive rats 7) support this notion. In addition, our study employing APA knockout mice has demonstrated more direct evidence of APA involvement of BP regulation.…”

Section: Renin-angiotensin System (Ras) and Apamentioning

confidence: 94%

Role of Aminopeptidases in the Blood Pressure Regulation

Mitsui

Nomura

Itakura

et al. 2004

Biological & Pharmaceutical Bulletin

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In addition to the neural and autoregulatory factors, blood pressure (BP) is regulated by humoral factors including vasoactive peptides. When evaluating the peptide actions, degradation by proteases should be also considered in addition to the generation of peptides and their receptors. This review describes the roles of aminopeptidase A, placental leucine aminopeptidase and kininase I, which are enzymes responsible for hydrolyzing angiotensin II (AngII), vasopressin (AVP) and bradykinin (BK), respectively, in BP regulation. Especially, we focus on the association of the proteases with preeclampsia, hypertensive disorder peculiar to pregnancy, since one of the representative organs that are rich in theses proteases is placenta. Although the physiological roles of the placental proteases have not been fully understood, several lines of evidence suggest that the proteases are involved in the maintenance of pregnancy homeostasis including fetal and maternal BP regulation through the metabolism of bioactive peptides at the interface between mother and fetus.

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“…Over the course of many years, the nature of so-called 'angiotensinase' has been stud ied [16][17][18][19]. It has been widely accepted that 'angiotensinase' is not a single enzyme but includes many enzymes such as aminopepti dase M (EC 3.4.11.2), cystine aminopepti dase (EC 3.4.11.3) and aminopeptidase A (EC 3.4.11.7).…”

Section: Discussionmentioning

confidence: 99%

Purification and Characterization of Human Placental Aminopeptidase A

Yamada¹,

Mizutani²,

Kurauchi³

et al. 1988

Enzyme

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Human placental aminopeptidase A (AAP) was purified 3,900-fold from human placenta and characterized. The enzyme was solubilized from membrane fractions with Triton X-100, then subjected to trypsin digestion, zinc sulfate fractionation, chromatographies with DE-52, Sephacryl S-300, and hydroxylapatite, affinity chromatography with Bestatin- Sepharose 4B, and finally immunoaffinity chromatography with the antibody against microsomal leucine aminopeptidase (LAP). Aminopeptidase A was completely separated from leucine aminopeptidase by the immunoaffinity chromatography. The apparent relative molecular mass (Mr) of the enzyme was estimated to be 280,000 by gel filtration. The purified enzyme was most active at pH 7.1 with L-aspartyl-ß-naphthylamide (L-Asp-NA) as substrate; the K(m) value for this substrate was 4.0 mmol/l in the presence of Ca2+. Human placental aminopeptidase A was markedly activated by alkaline earth metals (Ca^2+, Sr^2+, Ba^2+), but strongly inhibited by metal chelating agents such as EDTA and ο-phenanthroline. The highest activity was observed with L-glutamyl-ß-naphthylamide, while only minimal hydrolysis was found with some neutral and basic amino acid ß-naphthylamides.

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Human placental leucine aminopeptidase (P-LAP) as a hypotensive agent

Cited by 14 publications

References 12 publications

Quantitative high-throughput profiling of snake venom gland transcriptomes and proteomes (Ovophis okinavensis and Protobothrops flavoviridis)

Quantitative high-throughput profiling of snake venom gland transcriptomes and proteomes (Ovophis okinavensis and Protobothrops flavoviridis)

Role of Aminopeptidases in the Blood Pressure Regulation

Purification and Characterization of Human Placental Aminopeptidase A

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