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

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.

Abbreviations

cGMP:

cyclic guanosine monophosphate

CREB:

cAMPresponsive element binding protein

ERK:

extracellular signal-regulated kinase

MAPK:

mitogen-activated protein kinase

NGF:

nerve growth factor

NO:

nitric oxide

NOS:

nitric oxide synthase

PI3K:

phosphatidylinositol 3-kinase

SNP:

sodium nitroprusside

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Correspondence to József Szeberényi.

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Bátor, J., Varga, J., Berta, G. et al. Sodium nitroprusside, a nitric oxide donor, fails to bypass the block of neuronal differentiation in PC12 cells imposed by a dominant negative Ras protein. Cell Mol Biol Lett 17, 323–332 (2012). https://doi.org/10.2478/s11658-012-0013-8

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  • DOI: https://doi.org/10.2478/s11658-012-0013-8

Key words

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