Document Detail


Disrupted cell cycle arrest and reduced proliferation in corneal fibroblasts from GCD2 patients: A potential role for altered autophagy flux.
MedLine Citation:
PMID:  25450621     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
This study investigates the role of impaired proliferation, altered cell cycle arrest, and defective autophagy flux of corneal fibroblasts in granular corneal dystrophy type 2 (GCD2) pathogenesis. The proliferation rates of homozygous (HO) GCD2 corneal fibroblasts at 72h, 96h, and 120h were significantly lower (1.102±0.027, 1.397±0.039, and 1.527±0.056, respectively) than those observed for the wild-type (WT) controls (1.441±0.029, 1.758±0.043, and 2.003±0.046, respectively). Flow cytometry indicated a decreased G1 cell cycle progression and the accumulation of cells in the S and G2/M phases in GCD2 cells. These accumulations were associated with decreased levels of Cyclin A1, B1, and E1, and increased expression of p16 and p27. p21 and p53 expression was also significantly lower in GCD2 cells compared to the WT. Interestingly, treatment with the autophagy flux inhibitor, bafilomycin A1, resulted in similarly decreased Cyclin A1, B1, D1, and p53 expression in WT fibroblasts. Furthermore, similar findings, including a decrease in Cyclin A1, B1, and D1 and an increase in p16 and p27 expression were observed in autophagy-related 7 (Atg7; known to be essential for autophagy) gene knockout cells. These data provide new insight concerning the role of autophagy in cell cycle arrest and cellular proliferation, uncovering a number of novel therapeutic possibilities for GCD2 treatment.
Authors:
Seung-Il Choi; Shorafidinkhuja Dadakhujaev; Yong-Sun Maeng; So-Yeon Ahn; Tae-Im Kim; Eung Kweon Kim
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-25
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  -     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Inc.
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