Fibroblast growth factor 2 applied to the optic nerve after axotomy increases Bcl-2 and decreases Bax in ganglion cells by activating the extracellular signal-regulated kinase signaling pathway

Wilson Ríos-Muñoz, Ileana Soto, Mildred V. Duprey-Díaz, Jonathan Blagburn, Rosa E. Blanco

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

We have shown that application of basic fibroblast growth factor (FGF-2) to axotomized optic nerve promotes the survival of frog retinal ganglion cells (RGCs). In the present study we used western blotting and immunocytochemistry to investigate the effects of this FGF-2 treatment upon the activation of the extracellular signal-regulated kinase (ERK) pathway, the amounts and distribution of Bcl-2 family proteins, and the activation of caspase-3. Axotomy alone temporarily increased ERK activation; FGF-2 treatment to the nerve prolonged this activation. This effect was blocked by U0126, a selective ERK kinase (MEK) inhibitor. Axotomy caused a decrease in Bcl-2 and a small increase in Bcl-xL. FGF-2 treatment caused an ERK-dependent increase in Bcl-2 and an ERK-independent increase in Bcl-xL. The pro-apoptotic Bax was increased by axotomy; FGF-2 treatment greatly decreased Bax levels, an effect that was inhibited by U0126. Axotomy induced the cleavage of caspase-3; FGF-2 treatment blocked this effect in an ERK-dependent manner. Finally, intraocular application of the MEK inhibitor caused a large reduction in the survival-promoting effect that FGF-2 application to the nerve stump had on RGCs. Our results suggest that FGF-2 acts, at least in part, via the ERK pathway to prevent apoptosis of axotomized RGCs not only by increasing amounts of anti-apoptotic proteins, but also by a striking reduction in the levels of apoptotic effectors themselves.

Original languageEnglish (US)
Pages (from-to)1422-1433
Number of pages12
JournalJournal of Neurochemistry
Volume93
Issue number6
DOIs
StatePublished - Jun 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Fibroblast growth factor 2 applied to the optic nerve after axotomy increases Bcl-2 and decreases Bax in ganglion cells by activating the extracellular signal-regulated kinase signaling pathway'. Together they form a unique fingerprint.

Cite this