Structural Organization of the 5′-End and Chromosomal Assignment of Human Placental Leucine Aminopeptidase/Insulin-Regulated Membrane Aminopeptidase Gene

Horio, Jun; Nomura, Seiji; Okada, Mayumi; Katsumata, Yuki; Nakanishi, Yoshinobu; Kumano, Yoshiharu; Takami, Shinichi; Kinoshita, Moritoshi; Tsujimoto, Masafumi; Nakazato, Hiroshi; Mizutani, Shigehiko

doi:10.1006/bbrc.1999.1184

Cited by 34 publications

(13 citation statements)

References 31 publications

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“…IRAP was formerly known as gp160 and vp165 and was used to designate an enzyme in the rat. Cystein aminopeptidase or oxytocinase (Otase) (EC 3.4.11.3) are considered as the human variant of IRAP since there is an 87% homology of their amino acid sequences [157,[162][163][164][165]. In turn, Otase was found to be identical to placental leucine aminopeptidase (P-LAP) [166], a major human placental protease.…”

Section: Insulin-regulated Aminopeptidase Corresponds To the At 4 Recmentioning

confidence: 99%

Involvement of insulin-regulated aminopeptidase in the effects of the renin–angiotensin fragment angiotensin IV: a review

et al. 2007

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For decades, angiotensin (Ang) II was considered as the end product and the only bioactive peptide of the renin-angiotensin system (RAS). However, later studies revealed biological activity for other Ang fragments. Amongst those, Ang IV has drawn a lot of attention since it exerts a wide range of central and peripheral effects including the ability to enhance learning and memory recall, anticonvulsant and anti-epileptogenic properties, protection against cerebral ischemia, activity at the vascular level and an involvement in atherogenesis. Some of these effects are AT(1) receptor dependent but others most likely result from the binding of Ang IV to insulin-regulated aminopeptidase (IRAP) although the exact mechanism(s) of action that mediate the Ang IV-induced effects following this binding are until now not fully known. Nevertheless, three hypotheses have been put forward: since Ang IV is an inhibitor of the catalytic activity of IRAP, its in vivo effects might result from a build-up of IRAP's neuropeptide substrates. Second, IRAP is co-localized with the glucose transporter GLUT4 in several tissue types and therefore, Ang IV might interact with the uptake of glucose. A final and more intriguing hypothesis ascribes a receptor function to IRAP and hence an agonist role to Ang IV. Taken together, it is clear that further work is required to clarify the mechanism of action of Ang IV. On the other hand, a wide range of studies have made it clear that IRAP might become an important target for drug development against different pathologies such as Alzheimer's disease, epilepsy and ischemia.

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Section: Insulin-regulated Aminopeptidase Corresponds To the At 4 Recmentioning

confidence: 99%

Involvement of insulin-regulated aminopeptidase in the effects of the renin–angiotensin fragment angiotensin IV: a review

et al. 2007

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“…Adipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases [Shipp and Look, 1993;Hattori et al, 1999;Matsumoto et al, 2000]. The ALAP gene is located on human chromosome 5q15, close to the leucyl/cystinyl aminopeptidase gene (LNPEP; MIM# 151300) [Horio et al, 1999;Rasmussen et al, 2000], which suggests a recent gene duplication .…”

Section: Introductionmentioning

confidence: 99%

Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension

et al. 2002

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Adipocyte-derived leucine aminopeptidase (ALAP) inactivates angiotensin II and/or generates bradykinin in the kidney, suggesting a possible role for ALAP in the regulation of blood pressure. We considered the hypothesis that genomic variants of the ALAP gene are associated with hypertension or individual variations in blood pressure. We screened for mutations in the ALAP gene in 48 unrelated Japanese individuals and identified 33 polymorphisms including 15 novel polymorphisms. We then performed a two-stage analysis. In the first stage, the eight missense polymorphisms were evaluated for associations with blood pressure in 96 apparently healthy individuals. In the second stage, only the most promising polymorphisms were evaluated for association with essential hypertension in 143 hypertensive and 348 normotensive subjects. Among the eight missense polymorphisms, the Ile276Met and Lys528Arg polymorphisms showed significant association with blood pressure. Subsequent analysis confirmed association between the Lys528Arg polymorphism and essential hypertension. The estimated odds ratio for essential hypertension was 2.3 for presence of the Arg allele at codon 528, in comparison with presence of the Lys/Lys genotype (P = 0.004). These findings support involvement of ALAP in the regulation of blood pressure.

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“…We have shown that although de novo additional protein synthesis was required, IL-1beta up-regulates P-LAP expression both at the mRNA and protein levels . Our laboratory has further discovered that P-LAP is located on chromosome 5q14.2-q15 (Horio et al, 1999).…”

Section: Factors Regulating Aminopeptidasesmentioning

confidence: 93%

A new approach regarding the treatment of preeclampsia and preterm labor

Mizutani¹,

Wright

Kobayashi

2011

Life Sciences

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Structural Organization of the 5′-End and Chromosomal Assignment of Human Placental Leucine Aminopeptidase/Insulin-Regulated Membrane Aminopeptidase Gene

Cited by 34 publications

References 31 publications

Involvement of insulin-regulated aminopeptidase in the effects of the renin–angiotensin fragment angiotensin IV: a review

Involvement of insulin-regulated aminopeptidase in the effects of the renin–angiotensin fragment angiotensin IV: a review

Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension

A new approach regarding the treatment of preeclampsia and preterm labor

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