Open Access

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 Bátor1,
  • Judit Varga1,
  • Gergely Berta1,
  • Tamar Barbakadze2,
  • David Mikeladze2,
  • Jeremy Ramsden3 and
  • József Szeberényi1Email author
Cellular & Molecular Biology LettersAn International Journal201217:13

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

Received: 29 July 2011

Accepted: 27 March 2012

Published: 10 April 2012

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.

Key words

Nitric oxideSodium nitroprussidePC12 cellsNerve growth factorNeuronal differentiationDominant inhibitory Ras proteinp53 proteinERK proteinsAkt proteinCREB protein

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