Membrane-Bound Cell Surface Peptidases in Reproductive Organs.

Fujiwara, Hiroshi; Imai, Kimitoshi; Inoue, Takuya; Maeda, Masako; Fujii, Shingo

doi:10.1507/endocrj.46.11

Cited by 28 publications

(12 citation statements)

References 88 publications

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“…The membrane-bound peptidases are widely distributed in various tissues and cell types, such as hematopoietic cells, renal tubules, small intestine, vascular Brought to you by | Purdue University Libraries Authenticated Download Date | 6/2/15 11:12 PM endothelial cells or pericytes, and female reproductive organs including placenta, ovary and uterus (Shipp and Look, 1993;Fujiwara et al, 1999). Recent studies have demonstrated that these peptidases are expressed not only in normal cells but also in neoplastic cells in a variety of human malignancies (Iwata and Morimoto, 1999;Nanus, 2003).…”

Section: Structure General Function and Tissue Distribution Of Membrmentioning

confidence: 99%

“…In female reproductive organs, NEP is functionally expressed in human placenta and uterine endometrial stromal cells (Fujiwara et al, 1999). We demonstrated that NEP is expressed in placental syncytiotrophoblasts (differentiated trophoblasts), and may be involved in regulating the secretion of human chorionic gonadotropin Brought to you by | Purdue University Libraries Authenticated Download Date | 6/2/15 11:12 PM (hCG) by degradation of GnRH .…”

Section: Neutral Endopeptidase (Nep/cd10 Neprilysin Ec 342411)mentioning

confidence: 99%

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Regulatory role of membrane-bound peptidases in the progression of gynecologic malignancies

Ino

Shibata

Kajiyama

et al. 2004

Biological Chemistry

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Membrane-bound peptidases play a key role in the control of growth, differentiation, and signal transduction of many cellular systems by degrading bioactive peptides. Thus, abnormal changes in their expression pattern and catalytic function result in altered peptide activation, which contributes to neoplastic transformation or progression. In this review, we describe our recent findings along with work from other groups on the expression and biological functions of membrane-bound peptidases in cancer, focusing on the regulatory roles of three peptidases, aminopeptidase A (APA), neutral endopeptidase (NEP) and placental leucine aminopeptidase (P-LAP), in the progression of gynecologic malignancies. APA, NEP and P-LAP are differentially expressed and localized in various gynecologic malignancies including cervical cancer, endometrial cancer, ovarian cancer and choriocarcinoma in a tumor-type specific pattern. The expression levels are up- or down-regulated depending on histological grade or disease progression. These peptidases play regulatory roles in tumor cell proliferation, invasion or angiogenesis via degradation/inactivation of target peptides such as angiotensin II, endothelin-1 and oxytocin, which act on cancer cells as stimulatory or inhibitory factors. Thus, membrane-bound peptidases may become not only a new diagnostic/prognostic marker, but also a novel molecular target for the treatment of gynecologic malignancies.

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Section: Structure General Function and Tissue Distribution Of Membrmentioning

confidence: 99%

Section: Neutral Endopeptidase (Nep/cd10 Neprilysin Ec 342411)mentioning

confidence: 99%

Regulatory role of membrane-bound peptidases in the progression of gynecologic malignancies

Ino

Shibata

Kajiyama

et al. 2004

Biological Chemistry

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“…Aminopeptidase A and aminopeptidase N belong to the class of membrane-bound cell surface peptidases, which have extracellular catalytic sites and can metabolize biologically active peptides at the cell surface, serving as local regulators of peptide concentrations (72). An additional member of this group of enzymes is neutral endopeptidase, which recently was identified as a major A␤1-42-catabolizing enzyme (73 (75).…”

Section: Amino-terminal-and Carboxyl-terminal-truncated A␤ Species Inmentioning

confidence: 99%

Elevation of β-Amyloid Peptide 2–42 in Sporadic and Familial Alzheimer's Disease and Its Generation in PS1 Knockout Cells

Wiltfang¹,

Esselmann²,

Cupers³

et al. 2001

Journal of Biological Chemistry

120

123

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show a decrease of all secreted A␤ peptide species, as expected, because this mutant is processed mainly by ␣-secretase. This drop is even more pronounced for the APP-KK construct (APP mutant carrying an endoplasmic reticulum retention motif). Surprisingly, A␤2-42 is significantly less affected in PS1؊/؊ neurons and in neurons transfected with the endocytosis-deficient APP-⌬ct construct. Our data confirm that PS1 is closely involved in the production of A␤1-40/42 and the carboxyl-terminal-truncated A␤1-37, A␤1-38, and A␤1-39, but the amino-terminaltruncated and carboxyl-terminal-elongated A␤2-42 seems to be less affected by PS1 deficiency. Moreover, our results indicate that the latter A␤ peptide species could be generated by a ␤ Asp/Ala -secretase activity.

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“…In the intestinal brush-border membranes it participates in the ¢nal steps of digestion by cleaving peptides into their constituent amino acids. APN is also found in reproductive organs (Fujiwara et al, 1999), and is very abundant in the kidney where it appears to cleave peptides, thereby preventing their reentry into the vasculature (Hersh et al, 1987). At the renal brush-border membrane level, APN has been suggested to act as anion exchanger.…”

mentioning

confidence: 99%

First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor [125I]RB 129

et al. 2001

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The selective and potent aminopeptidase N inhibitor [125I]RB 129 has been used for the radioautographic localization of this enzyme in rat brain, spinal cord and intestine. Brain microvessels and intestine brush-border cells were shown to present a high concentration of aminopeptidase N. Moreover, a labeling of various brain structures was observed. A very high level of binding occurred in the meninges, choroid plexus, pineal gland, paraventricular nucleus and pituitary gland. Moderate to high labeling was also observed in the cortex, caudate-putamen, subthalamic nucleus, central periaqueductal gray, thalamus, as well as in the dorsal and ventral horn of the spinal cord, which are known to contain a high concentration of enkephalins, opioid receptors and neutral endopeptidase. This co-localization confirms the physiological implication of aminopeptidase N in the inactivation of enkephalins accounting for the requirement of dual inhibition of neutral endopeptidase and aminopeptidase N to observe highly significant morphine-like effects induced by the protected endogenous opioid peptides. Aminopeptidase N was also visualized in moderate to high levels in other brain structures such as the hippocampus, nucleus accumbens, substantia nigra, hypothalamus (dorsomedial and ventromedial nuclei), raphe nucleus, pontine nucleus, inferior olive, and in high concentration in the granular layer of cerebellum. In summary, aminopeptidase N has been visualized for the first time in numerous brain areas using the selective inhibitor [125I]RB 129. This iodinated probe could allow the ex vivo and in vivo localization of aminopeptidase N in various tissues to be investigated and may also be used to evaluate quantitative changes in aminopeptidase N expression in pathological situations. Aminopeptidase N, which preferably removes NH2-terminal neutral amino acids from peptides, has probably a host of substrates. Nevertheless, a certain in vivo selectivity could be achieved by the presence of the enzyme in structures where the peptide effector and its receptors are also co-localized.

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Membrane-Bound Cell Surface Peptidases in Reproductive Organs.

Cited by 28 publications

References 88 publications

Regulatory role of membrane-bound peptidases in the progression of gynecologic malignancies

Regulatory role of membrane-bound peptidases in the progression of gynecologic malignancies

Elevation of β-Amyloid Peptide 2–42 in Sporadic and Familial Alzheimer's Disease and Its Generation in PS1 Knockout Cells

First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor [125I]RB 129

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