Cloning and Characterization of cDNA Encoding a Precursor for Human Adrenomedullin

Kïtamura, Kazuo; Sakata, Junichiro; Kangawa, Kenji; Kojima, Masayasu; Matsuo, Hisayuki; Eto, Tanenao

doi:10.1006/bbrc.1993.1881

Cited by 581 publications

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“…The precursor of human AM (human preproAM) comprises 185 amino acids and includes the AM sequence [ 8 ]. In addition to AM, proadrenomedullin (proAM) contains a novel 20-residue peptide called proadrenomedullin N-terminal 20 peptide (PAMP), which is also processed from the AM precursor ( Fig.…”

Section: Basic Characteristics Of Ammentioning

confidence: 99%

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Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis

Kïtamura

Ashizuka

Inatsu

et al. 2015

Innovative Medicine

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Adrenomedullin (AM) was originally isolated from human pheochromocytoma as a biologically active peptide with potent vasodilating action, but it also has a wide range of physiological properties including cardiovascular protection, neovascularization, and the ability to suppress apoptosis. It is constitutively produced by various tissues including the gastrointestinal tract. AM production and secretion can be induced by pro-infl ammatory cytokines such as tumor necrosis factor-α and interleukin-1, as well as by lipopolysaccharide. Conversely, AM causes the downregulation of infl ammatory cytokines in cultured cells and downregulates inflammatory processes in various models of colitis, including those induced by acetic acid and by dextran sulfate sodium. AM works by exerting anti-infl ammatory and antibacterial effects and by stimulating mucosal regeneration and supporting maintenance of the colonic epithelial barrier. The present fi ndings suggest that AM could serve as a novel agent for treating refractory ulcerative colitis.

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Section: Basic Characteristics Of Ammentioning

confidence: 99%

“…When processed from preproAM, AM-Gly, an intermediate form (iAM), is produced and converted by an amidation enzyme to mature AM (mAM) with an amide structure at the C-terminal [ 8 ]. The mature form of PAMP is thought to be produced via a similar process.…”

Section: Figmentioning

confidence: 99%

Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis

Kïtamura

Ashizuka

Inatsu

et al. 2015

Innovative Medicine

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“…28 Cells were harvested from culture, washed and resuspended in complete medium. Cells were plated in quadruplicate in 100 cm 2 Petri dishes (Falcon; Becton Dickinson, Lakeridge, NJ) and cultured overnight. The number of cells per plate was selected so that more than 100 colonies were obtained in the control group.…”

Section: Colony Formation Assaymentioning

confidence: 99%

“…Expression of adrenomedullin, an amidated peptide that was originally isolated from human pheochromocytoma, 2 has been documented in both the human and rat prostate, 3 human prostate carcinoma 4 and prostate cancer cell lines, 4 where it has been suggested that adrenomedullin (AM) may act as an autocrine/ paracrine factor. Human AM consists of 52 amino acids (50 amino acids for rat AM) and shares certain homology with the calcitonin gene-related peptide (CGRP).…”

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confidence: 99%

Gene expression profiling identifies IL‐13 receptor α2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin

Gonzalez-Moreno

Calvo

Joshi

et al. 2004

Intl Journal of Cancer

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Human adrenomedullin (AM) is a 52 amino acid peptide, which shares homology with the calcitonin gene-related peptide. Overexpression of AM in the prostate carcinoma cell line PC-3 results in growth inhibition with a 20% (for human AM) and 35% (for rat AM) increase in doubling time compared to parental or mocktransfected cells. We demonstrate by gene expression profiling that AM overexpression results in the dysregulation of approximately 100 genes. Examples of such genes include many involved in the formation of the cytoskeleton, cell adhesion and the extracellular matrix, as well as regulators of the cell cycle and apoptosis, cytokines and transcription factors. Several genes related to cell growth arrest, such as GADD45, IGF-BP6 and RUNX-3, are upregulated by AM. Interestingly, interleukin-13 receptor ␣2 (IL-13R␣2) transcripts were significantly increased in clones overexpressing AM, which was confirmed by semiquantitative RT-PCR analysis. In addition, PC-3 cells treated with AM showed an overexpression of IL-13R␣2, which was abolished when cells were preincubated with an anti-AM blocking antibody. When PC-3 cells overexpressing AM and the IL-13R␣2 were treated with the highly specific IL13-PE38 cytotoxin, which binds to this receptor, a concentration-dependent inhibition of protein synthesis was observed. The IC 50 (concentration of cytotoxin inhibiting protein synthesis by 50%) ranged from 1 to 4 ng/ml. This cytotoxicity was specific as it was neutralized by the excess of IL-13 and confirmed by clonogenic assays. This study describes a novel AM-induced mechanism of tumor sensitization through the upregulation of functional IL-13R␣2 chain, an ideal target for the highly specific recombinant chimeric cytotoxin IL13-PE38. © 2004 Wiley-Liss, Inc.Key words: cDNA microarrays; prostate cancer; adrenomedullin; IL-13R␣2; gene expression profiling Prostate carcinoma is the second leading cause of cancer mortality among men in the United States. 1 The 5-year relative survival rate for the patients whose tumors are diagnosed with local or regional disease approaches 100%, but the relative 10-and 15-year survival rates are reduced to 75% and 54%, respectively. 1 Although localized prostate cancer may be successfully treated, 70% of patients eventually progress and develop metastasis. The current nonsurgical therapeutic regimens for treating prostate carcinoma include radio-, hormonal-and chemotherapy, as well as a combination of these regimens, depending on specific circumstances of the patient. The limited success of treating particular forms of prostate cancer requires that additional targets for therapy be identified and tested.Expression of adrenomedullin, an amidated peptide that was originally isolated from human pheochromocytoma, 2 has been documented in both the human and rat prostate, 3 human prostate carcinoma 4 and prostate cancer cell lines, 4 where it has been suggested that adrenomedullin (AM) may act as an autocrine/ paracrine factor. Human AM consists of 52 amino acids (50 amino acids for rat AM) and shar...

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“…Adrenomedullin (ADM) and its gene-related peptide proadrenomedullin N-terminal 20 peptide (PAMP) are derived from a 185-amino acid precursor molecule [12,14,39]. Originally isolated from pheochromocytoma, ADM has been localized to the adrenal gland, lung, cardiac ventricle, kidney, pancreas, and brain, especially the thalamus and hypothalamus [7,30].…”

Section: Introductionmentioning

confidence: 99%

Proadrenomedullin NH2-terminal 20 peptide (PAMP) and adrenomedullin bind to teratocarcinoma cells☆

et al. 2000

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Proadrenomedullin NH 2-terminal 20 peptide (PAMP) and adrenomedullin (ADM) bind to teratocarcinoma cells. The effects of PAMP and ADM on teratocarcinoma cells were investigated. 125 I-PAMP bound to PA1 cells with moderate affinity (K d ϭ 110 nM) to a single class of sites (B max ϭ 110 000/cell). Specific 125 I-PAMP binding was inhibited by PAMP (IC 50 of 100 nM) but not ADM, calcitonin gene-related peptide (CGRP), or amylin. Specific 125 I-ADM binding was inhibited with high affinity by ADM, CGRP, and CGRP(8 -37) (IC 50 values of 10, 10, and 15 nM respectively) but not PAMP or amylin. ADM elevated cAMP (ED 50 value of 100 nM), whereas PAMP had no effect on basal cAMP but inhibited the increase in cAMP caused by 10 nM ADM. Also, the increase in cAMP caused by ADM was inhibited CGRP(8 -37), suggesting that ADM is binding to CGRP receptors. ADM (100 nM) stimulated transiently c-fos mRNA, whereas PAMP (1000 nM) had little effect; however, PAMP inhibited the increase in c-fos mRNA caused by ADM. ADM stimulated [ 3 H]thymidine uptake into PA1 cells, whereas PAMP inhibited the increase in thymidine uptake caused by ADM. These results indicate that ADM and PAMP are both biologically active in teratocarcinoma cells. Published by Elsevier Science Inc.

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Cloning and Characterization of cDNA Encoding a Precursor for Human Adrenomedullin

Cited by 581 publications

References 0 publications

Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis

Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis

Gene expression profiling identifies IL‐13 receptor α2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin

Proadrenomedullin NH2-terminal 20 peptide (PAMP) and adrenomedullin bind to teratocarcinoma cells☆

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