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Differential expression of adrenomedullin and its receptor component, receptor activity modifying protein (RAMP) 2 during hypoxia in cultured human neuroblastoma cells.

Abstract
Adrenomedullin is a potent vasodilator peptide originally isolated from a pheochromocytoma. Recently, a novel adrenomedullin receptor has been identified as a complex consisting of calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP) 2. To explore possible pathophysiological roles of adrenomedullin and its receptor component RAMP2 in hypoxic tissues, we studied effects of hypoxia on expression of adrenomedullin and RAMP2 in two human neuroblastoma cell lines, IMR-32 and NB69, by radioimmunoassay and Northern blot analysis. Expression levels of adrenomedullin were increased by hypoxia in both cell lines. Treatment with cobalt chloride or desferrioxamine mesylate also increased expression levels of adrenomedullin mRNA. On the other hand, expression levels of RAMP2 mRNA were decreased in IMR-32 cells and were not changed in NB69 cells by hypoxia. Treatment with cobalt chloride or desferrioxamine mesylate decreased expression levels of RAMP2 mRNA in both IMR-32 and NB69 cells. These findings indicate that adrenomedullin expression is induced during hypoxia in IMR-32 and NB69 neuroblastoma cells, but RAMP2 expression is rather suppressed under the same conditions. The decreased expression of RAMP2 and the ADM expression induction under hypoxia may constitute one mechanism of cellular adaptation to hypoxic stress.
AuthorsT Kitamuro, K Takahashi, K Totsune, M Nakayama, O Murakami, W Hida, K Shirato, S Shibahara
JournalPeptides (Peptides) Vol. 22 Issue 11 Pg. 1795-801 (Nov 2001) ISSN: 0196-9781 [Print] United States
PMID11754965 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antimutagenic Agents
  • Intracellular Signaling Peptides and Proteins
  • Iron Chelating Agents
  • Membrane Proteins
  • Peptides
  • RAMP2 protein, human
  • Receptor Activity-Modifying Protein 2
  • Receptor Activity-Modifying Proteins
  • Receptors, Adrenomedullin
  • Receptors, Peptide
  • Adrenomedullin
  • Cobalt
  • cobaltous chloride
  • Deferoxamine
Topics
  • Adrenomedullin
  • Antimutagenic Agents (pharmacology)
  • Cell Hypoxia
  • Cobalt (pharmacology)
  • Deferoxamine (pharmacology)
  • Gene Expression (drug effects)
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Iron Chelating Agents (pharmacology)
  • Membrane Proteins (biosynthesis)
  • Neuroblastoma (metabolism, pathology)
  • Peptides (metabolism)
  • Receptor Activity-Modifying Protein 2
  • Receptor Activity-Modifying Proteins
  • Receptors, Adrenomedullin
  • Receptors, Peptide (biosynthesis)
  • Tumor Cells, Cultured

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