Publication: Proadrenomedullin-derived peptides as
autocrine-paracrine regulators of cell growth
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Date
2001
Authors
Belloni, A. S. ; Albertin, G. ; Forneris, M. L. ; Nussdorfer, G. G.
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Proa dr e nomedullin (pADM )-d e ri ve d
peptides, adrenomedullin (ADM) and pADM N-terminal
20 peptide (PAMP), are hypotensive peptides, which are
expressed, along with their receptors, in several tissues
and orga ns, the function of which they regulate by acting
in an aut ocrin e-parac rin e mann er. Apart fr om th eir
involvement in the regul ation of blood pressure and fluid
and electro lyte homeostasis, pADM-deri ved peptides
appear to playa role in the modulation of cell and tissue
growth. Evid ence has bee n prov ided th at ADM: I)
favors th e remodeling of cardiovascular system under
path ologica l conditi ons, by exe rting an anti apoptotic
effect on endotheli al cells and an antiproliferogeni c and
antimi gratory acti on on vascul ar smooth-muscle ce lls
durin g neo intimal hype rpl asia, and by dec reasin g
proliferation and protein ynthesis of cardiac myoeytes
and fibrobl asts. These last two effects are mediated by
ca lc ito nin ge ne -re lated peptid e type 1 (CGRPI )
receptors coupled to the adenylate cycl ase (AC)/protein
kin ase ( PK) A-d epe nd e nt casca de; 2) inhi bits
prolife rati o n and e nh a nces apo pt osis of kidn ey
mesa ngial ce lls, through the modul ation of mi togenac ti va ted PK (MAPK ) casca des; 3) stimul ates
proliferation of adrenal zona glomerulosa ce lls, acting
via CG RPl rece ptor coupl ed to the tyrosin e kinase -
depend ent MAPK cascade, th e reby possibl y bein g
involved in the maintenance and stimulation of adrenal
growth ; 4) enhances proliferati on of skin and mucosa
epitheli al ce lls and fibrobl asts, by ac ti va ting CGRP]
receptor coupled to the AC/PKA signaling pathway; and
5) enh ances proli fe rati on of several tumor- ce ll lines
through the activa ti on of the AC/PKA cascade, which
suggests a pote nti a l role fo r ADM as promo te r of
neopl asti c growth. The growth effects of PAMP have
bee n fa r less investiga ted: findings indicate that this
peptide, like ADM. enhances adrenal zona glomerulosa ce ll proliferation, and, in contrast with ADM, depresses
DNA synthesis in some cancer-cell lines. Both pADMde ri ve d peptid es are th o ug ht to be invol ve d in
embryoge nesis, such a contention being based on the
demonstration of high pADM-gene expression during
the crucial phases of organ growth and differenti ation.
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Citation
Histology and histopathology, Vol. 16, nº 4 (2001)
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