STAT3 activation in photoreceptors by leukemia inhibitory factor is associated with protection from light damage.
J Neurochem
; 105(3): 784-96, 2008 May.
Article
en En
| MEDLINE
| ID: mdl-18088375
Members of the interleukin-6 cytokine family, including leukemia inhibitory factor (LIF), signal through gp130. The neuroprotective role of gp130 activation has been widely demonstrated in both CNS and PNS, but the mechanism by which this is accomplished is not well established. We investigated temporal and cell-specific activation of signaling pathways induced by LIF in the mature mouse retina. Intravitreal injection of LIF preserved photoreceptor function and prevented photoreceptor cell death from light-induced oxidative damage in a dose-dependent manner (2 days post-injection). A therapeutic dose of LIF induced rapid and sustained activation of signal transducer and activator of transcription (STAT) 3. Activated STAT3 was localized to all the retinal neurons and glial cells, including photoreceptors. Activation of extracellular signal-regulated kinase 1 and 2 was robust but transient in Müller glial cells, and undetectable at the time of light exposure. Akt was not activated by LIF. We also show that at the time of neuroprotection, STAT3 but not extracellular signal-regulated kinase 1 and 2 or the Akt pathways was active in LIF-treated retinas, and activated STAT3 was clearly localized in transcriptionally active areas of photoreceptor nuclei. Our data suggest that photoreceptor protection in response to LIF can be directly mediated by activation of STAT3 in photoreceptors.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Fotorreceptoras
/
Citoprotección
/
Factor de Transcripción STAT3
/
Factor Inhibidor de Leucemia
/
Luz
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Neurochem
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido