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CREB1/ATF1 activation in photoreceptor degeneration and protection
- Source :
- Investigative ophthalmologyvisual science. 50(11)
- Publication Year :
- 2009
-
Abstract
- The cAMP response element binding protein 1 (CREB1), activating transcription factor 1 (ATF1) and cAMP response element modulator (CREM) are closely related members of the CREB/ATF family. This family belongs to the basic leucine zipper (bZIP) superfamily of transcription factors, which include mammalian c-Fos, c-Jun, and c-Myc.1 When activated by phosphorylation, these transcription factors bind as homo- or heterodimers to a palindromic consensus sequence known as the cAMP-response element (CRE).1–3 CREB1/ATF1 are activated by a wide array of physiological stimuli including peptide hormones, growth factors, intracellular Ca2+,1 and cellular stress.4–7 In adult mammalian retina, p-CREB1 is normally limited to the ganglion cell and inner nuclear layers.8–11 It appears that as in other parts of the nervous system,12–14 stressful stimuli can induce phosphorylation of CREB1 in retinal neurons.8–10,15 In photoreceptors, expression is noted in cat and rabbit after retinal injury by detachment10 and in rat photoreceptors after penetrating trauma.8 In vitro, increased expression of pCREB in mouse photoreceptor-derived 661W cells in response to FGF suggests that CREB1 may be associated with a neuroprotective outcome in photoreceptors.16 The present study was conducted to determine whether CREB1/ATF1 can be phosphorylated in dog and human photoreceptors and whether this occurs in response to degenerative or protective stimuli. We describe the distribution of phosphorylated CREB1/ATF1 in canine models of retinitis pigmentosa (RP) and in human retinas with age-related macular degeneration (AMD). The association between CREB1/ATF1 phosphorylation and photoreceptor protection induced by ciliary neurotrophic factor (CNTF) was evaluated to assess whether CREB1/ATF1 is influenced by this neuroprotective stimulus.
- Subjects :
- Male
medicine.medical_specialty
Rhodopsin
genetic structures
Genotype
Immunoblotting
Cell Count
Ciliary neurotrophic factor
CREB
Immunoenzyme Techniques
Macular Degeneration
Dogs
Internal medicine
Retinitis pigmentosa
medicine
Animals
Humans
Ciliary Neurotrophic Factor
Dog Diseases
Phosphorylation
Cyclic AMP Response Element-Binding Protein
Transcription factor
Aged
Activating Transcription Factor 1
Aged, 80 and over
Retina
Arrestin
biology
ATF1
Articles
medicine.disease
Cell biology
medicine.anatomical_structure
Endocrinology
biology.protein
Female
sense organs
Signal transduction
CREB1
Retinitis Pigmentosa
Photoreceptor Cells, Vertebrate
Subjects
Details
- ISSN :
- 15525783
- Volume :
- 50
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Investigative ophthalmologyvisual science
- Accession number :
- edsair.doi.dedup.....1ecd74d64773a78eca4d3f3cbae13d1c