RGD Reference Report - Chaperone peptides of a-crystallin inhibit epithelial cell apoptosis, protein insolubilization, and opacification in experimental cataracts. - Rat Genome Database

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Chaperone peptides of a-crystallin inhibit epithelial cell apoptosis, protein insolubilization, and opacification in experimental cataracts.

Authors: Nahomi, Rooban B  Wang, Benlian  Raghavan, Cibin T  Voss, Oliver  Doseff, Andrea I  Santhoshkumar, Puttur  Nagaraj, Ram H 
Citation: Nahomi RB, etal., J Biol Chem. 2013 May 3;288(18):13022-35. doi: 10.1074/jbc.M112.440214. Epub 2013 Mar 18.
RGD ID: 13782357
Pubmed: PMID:23508955   (View Abstract at PubMed)
PMCID: PMC3642345   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M112.440214   (Journal Full-text)

α-Crystallin is a member of the small heat-shock protein (sHSP) family and consists of two subunits, αA and αB. Both αA- and αB-crystallin act as chaperones and anti-apoptotic proteins. Previous studies have identified the peptide (70)KFVIFLDVKHFSPEDLTVK(88) in αA-crystallin and the peptide (73)DRFSVNLDVKHFSPEELKVK(92) in αB-crystallin as mini-chaperones. In the human lens, lysine 70 (Lys(70)) of αA and Lys(92) of αB (in the mini-chaperone sequences) are acetylated. In this study, we investigated the cellular effects of the unmodified and acetyl mini-chaperones. The αA- and αB-crystallin peptides inhibited stress-induced aggregation of four client proteins, and the αA-acetyl peptide was more effective than the native peptide against three of the client proteins. Both the acetyl and native crystallin peptides inhibited stress-induced apoptosis in two mammalian cell types, and this property was directly related to the inhibition of cytochrome c release from mitochondria and the activity of caspase-3 and -9. In organ-cultured rat lenses, the peptides inhibited calcimycin-induced epithelial cell apoptosis. Intraperitoneal injection of the peptides inhibited cataract development in selenite-treated rats, which was accompanied by inhibition of oxidative stress, protein insolubilization, and caspase activity in the lens. These inhibitory effects were more pronounced for acetyl peptides than native peptides. A scrambled αA-crystallin peptide produced no such effects. The results suggest that the α-crystallin chaperone peptides could be used as therapeutic agents to treat cataracts and diseases in which protein aggregation and apoptosis are contributing factors.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cataract treatmentISOCasp3 (Rattus norvegicus)13782357; 13782357 RGD 
cataract treatmentISOCasp9 (Rattus norvegicus)13782357; 13782357 RGD 
cataract treatmentIEP 13782357; 13782357 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casp3  (caspase 3)
Casp9  (caspase 9)

Genes (Mus musculus)
Casp3  (caspase 3)
Casp9  (caspase 9)

Genes (Homo sapiens)
CASP3  (caspase 3)
CASP9  (caspase 9)


Additional Information