Growth hormone releasing hormone induces the expression of nitric oxide synthase

Nektarios Barabutis, Agnieszka Siejka, Andrew V. Schally

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Growth hormone releasing hormone (GHRH) and its receptors are expressed in a wide variety of human tumours and established cancer cell lines and are involved in carcinogenesis. In addition, GHRH antagonists exert an antitumour activity in experimental cancer models. Recent studies indicate that the mechanisms involved in the mediation of the effects of GHRH include the regulation of the metabolism of the reactive oxygen species. This work demonstrates the expression of GHRH receptors and GHRH in the A549 human lung cancer cell line and shows that the mitogenic effect of GHRH in these cells is dependent on the activation of the extracellular receptor kinase (ERK)1/2 pathway. The action of GHRH can be suppressed by GHRH antagonist MZ-5-156 and mitogen activated protein kinase (MAPK) inhibitor PD 098059. These results are reflected in the effect in the proliferating cell nuclear antigen. In addition, our study shows that GHRH increases the expression of the inducible nitric oxide synthase, an enzyme which is strongly involved in various human diseases, including cancer and augments key intracellular regulators of its expression, such as pNF (nuclear factor)κBp50 and cyclooxygenase 2. GHRH antagonist MZ-5-156 counteracts the effects of GHRH in these studies, indicating that this class of peptide antagonists may be useful for the treatment of diseases related to increased oxidative and nitrosative stress.

Original languageEnglish (US)
Pages (from-to)1148-1155
Number of pages8
JournalJournal of Cellular and Molecular Medicine
Volume15
Issue number5
DOIs
StatePublished - May 1 2011

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Keywords

  • Growth factors
  • Nitrosative stress
  • Oxidative stress

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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