RGD Reference Report - Light-Induced photoreceptor degeneration in the mouse involves activation of the small GTPase Rac1. - Rat Genome Database

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Light-Induced photoreceptor degeneration in the mouse involves activation of the small GTPase Rac1.

Authors: Belmonte, MA  Santos, MF  Kihara, AH  Yan, CY  Hamassaki, DE 
Citation: Belmonte MA, etal., Invest Ophthalmol Vis Sci. 2006 Mar;47(3):1193-200.
RGD ID: 7775028
Pubmed: PMID:16505058   (View Abstract at PubMed)
DOI: DOI:10.1167/iovs.05-0446   (Journal Full-text)

PURPOSE: Rho GTPases play a central role in actin-based cytoskeleton reorganization, and they participate in signaling pathways that regulate gene transcription, cell cycle entry, and cell survival. This study verifies the role of Rac1 during light-induced retinal degeneration. METHODS: BALB/c mice were exposed to degenerative light stimulus, and their eyes were enucleated immediately or after the mice were kept in the dark for 6, 24, and 48 hours. Retinas were fixed and processed for immunohistochemical analysis. The distribution of Rac1 and its effectors-p21-activated kinases (PAKs) 1, 2, and 3-was studied by immunohistochemistry, whereas the expression of PAKs 3, 4, and 5 mRNA was analyzed by real-time PCR. Rac1 activity was measured using a pull-down assay. RESULTS: In control retinas, Rac1 was mostly observed in photoreceptors, plexiform layers, and Muller glial cells. In light-damaged retinas, some TUNEL-positive photoreceptors upregulated Rac1 expression. Conversely, most of the Rac1-positive cells were TUNEL-positive, mainly in early stages of retinal degeneration. The increase in Rac1 expression was preceded by enhanced Rac1 activity, detectable at the end of the light stimulus and still present 48 hours later. The distribution patterns of PAK1, PAK2, and PAK3 did not change in light-damaged retinas. However, there was a marked increase in PAK3 and PAK4 gene expression, whereas that of PAK5 mRNA remained the same. CONCLUSIONS: Rac1 may play a role in the apoptosis of light-damaged photoreceptors. The increased expression of PAK4 after light stimulus possibly functions as a protective mechanism against apoptosis.




  
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Evidence
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Original Reference(s)
PAK3Humanretinal degeneration  ISOPak3 (Mus musculus)mRNA and protein:increased expression:retinaRGD 
PAK4Humanretinal degeneration  ISOPak4 (Mus musculus)mRNA:increased expression:retinaRGD 
Pak3Ratretinal degeneration  ISOPak3 (Mus musculus)mRNA and protein:increased expression:retinaRGD 
Pak3Mouseretinal degeneration  IEP mRNA and protein:increased expression:retinaRGD 
Pak4Ratretinal degeneration  ISOPak4 (Mus musculus)mRNA:increased expression:retinaRGD 
Pak4Mouseretinal degeneration  IEP mRNA:increased expression:retinaRGD 


Genes (Rattus norvegicus)
Pak3  (p21 (RAC1) activated kinase 3) Pak4  (p21 (RAC1) activated kinase 4)

Genes (Mus musculus)
Pak3  (p21 (RAC1) activated kinase 3) Pak4  (p21 (RAC1) activated kinase 4)

Genes (Homo sapiens)
PAK3  (p21 (RAC1) activated kinase 3) PAK4  (p21 (RAC1) activated kinase 4)