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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
Author(s) -
RíosMuñoz Wilson,
Soto Ileana,
DupreyDíaz Mildred V.,
Blagburn Jonathan,
Blanco Rosa E.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03129.x
Subject(s) - axotomy , mapk/erk pathway , microbiology and biotechnology , fibroblast growth factor , basic fibroblast growth factor , biology , nerve growth factor , extracellular , signal transduction , chemistry , endocrinology , medicine , growth factor , biochemistry , receptor , regeneration (biology)
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‐x L . FGF‐2 treatment caused an ERK‐dependent increase in Bcl‐2 and an ERK‐independent increase in Bcl‐x L . 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.