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IGF‐I maintains calpastatin expression and attenuates apoptosis in several models of photoreceptor cell death
Author(s) -
Arroba Ana I.,
Wallace Deborah,
Mackey Ashley,
De La Rosa Enrique J.,
Cotter Thomas G.
Publication year - 2009
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.06902.x
Subject(s) - calpastatin , calpain , creb , retinitis pigmentosa , photoreceptor cell , apoptosis , microbiology and biotechnology , retinal degeneration , endocrinology , medicine , biology , chemistry , retina , transcription factor , neuroscience , biochemistry , gene , enzyme
Retinitis pigmentosa is a heterogeneous group of inherited retinal dystrophies in which the loss of photoreceptor cells via apoptosis leads to blindness. In this study we have experimentally mimicked this condition by treating 661W cells and wild‐type mouse retinal explants with a Ca 2+ ionophore. Ca 2+ overload induced apoptosis, which was correlated with calpain‐2 activation, loss of calpastatin, its endogenous inhibitor, as well as the loss of its transcriptional activator, phospho‐cAMP response element binding (CREB). All are similar changes to those observed in the rd1 mouse model of retinitis pigmentosa. Insulin like‐growth factor‐I (IGF‐I) attenuated this Ca 2+ ‐induced apoptosis, as well as decreased the activation of calpain‐2 and maintained calpastatin levels through the activation of the Akt‐CREB pathway. Similarly, IGF‐I decreased photoreceptor apoptosis in rd1 mouse retinal explants in parallel with reduced activation of calpain‐2 and increased levels of calpastatin and activation of phospho‐CREB. In conclusion, IGF‐I seems to protect neural cells following a physiopathological or an experimental increase in intracellular Ca 2+ , an observation that may have therapeutic consequences in neurodegenerative diseases such as retinitis pigmentosa.