Sodium nitroprusside, a nitric oxide donor, fails to bypass the block of neuronal differentiation in PC12 cells imposed by a dominant negative Ras protein

Judit Bátor, Judit Varga, Gergely Berta, Tamar Barbakadze, David Mikeladze, Jeremy Ramsden, József Szeberényi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Nitric oxide (NO) is a mediator of a diverse array of inter- and intracellular signal transduction processes. The aim of the present study was to analyze its possible role as a second messenger in the process of neuronal differentiation of PC12 pheochromocytoma cells. Upon NGF treatment wildtype PC12 cells stop dividing and develop neurites. In contrast, a PC12 subclone (designated M-M17-26) expressing a dominant-negative mutant Ras protein keeps proliferating and fails to grow neurites after NGF treatment. Sodium nitroprusside (SNP), an NO donor, was found to induce the p53 protein and to inhibit proliferation of both PC12 and M-M17-26 cells, but failed to induce neuronal differentiation in these cell lines. Key signaling pathways (the ERK and Akt pathways) were also not affected by SNP treatment, and the phosphorylation of CREB transcription factor was only slightly stimulated. It is thus concluded from the results presented in this paper that NO is unable to activate signaling proteins acting downstream or independent of Ras that are required for neuronal differentiation.

Original languageEnglish
Pages (from-to)323-332
Number of pages10
JournalCellular and Molecular Biology Letters
Volume17
Issue number3
DOIs
Publication statusPublished - Sep 2012

Keywords

  • Akt protein
  • CREB protein
  • Dominant inhibitory Ras protein
  • ERK proteins
  • Nerve growth factor
  • Neuronal differentiation
  • Nitric oxide
  • PC12 cells
  • Sodium nitroprusside
  • p53 protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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