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Decreased catalase expression and increased susceptibility to oxidative stress in primary cultured corneal fibroblasts from patients with granular corneal dystrophy type II.

Authors
 Seung-il Choi  ;  Tae-im Kim  ;  Kyu Seo Kim  ;  Bong-Yoon Kim  ;  So-yeon Ahn  ;  Hyun-ju Cho  ;  Hyung Keun Lee  ;  Hyun-Soo Cho  ;  Eung Kweon Kim 
Citation
 AMERICAN JOURNAL OF PATHOLOGY, Vol.175(1) : 248-261, 2009 
Journal Title
 AMERICAN JOURNAL OF PATHOLOGY 
ISSN
 0002-9440 
Issue Date
2009
MeSH
Adolescent ; Adult ; Blotting, Western ; Catalase/biosynthesis* ; Catalase/genetics ; Cells, Cultured ; Child ; Cornea/enzymology ; Cornea/physiopathology* ; Corneal Dystrophies, Hereditary/enzymology ; Corneal Dystrophies, Hereditary/genetics ; Corneal Dystrophies, Hereditary/physiopathology* ; Extracellular Matrix Proteins/biosynthesis ; Extracellular Matrix Proteins/genetics ; Female ; Fibroblasts/enzymology ; Fibroblasts/pathology* ; Flow Cytometry ; Humans ; Hydrogen Peroxide/metabolism ; Immunohistochemistry ; Male ; Middle Aged ; Oxidative Stress/physiology* ; RNA, Small Interfering ; Reactive Oxygen Species/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection ; Transforming Growth Factor beta/biosynthesis ; Transforming Growth Factor beta/genetics ; Young Adult
Abstract
Granular corneal dystrophy type II (GCD II) is an autosomal dominant disorder characterized by age-dependent progressive accumulation of transforming growth factor-beta-induced protein (TGFBIp) deposits in the corneal stroma. Several studies have suggested that corneal fibroblasts may decline with age in response to oxidative stress. To investigate whether oxidative stress is involved in the pathogenesis of GCD II, we assayed antioxidant enzymes, oxidative damage, and susceptibility to reactive oxygen species-induced cell death in primary cultured corneal fibroblasts (PCFs) from GCD II patients and healthy subjects. We found elevated protein levels of Mn-superoxide dismutase, Cu/Zn-superoxide dismutase, glutathione peroxidase, and glutathione reductase, as well as increased CAT mRNA and decreased catalase protein in GCD II PCFs. Furthermore, catalase is down-regulated in normal PCFs transfected with transforming growth factor-beta-induced gene-h3. We also observed an increase in not only intracellular reactive oxygen species and H(2)O(2) levels, but also malondialdehyde, 4-hydroxynonenal, and protein carbonyls levels in GCD II PCFs. Greater immunoreactivity for malondialdehyde was observed in the corneal tissue of GCD II patients. In addition, we observed a decrease in Bcl-2 and Bcl-xL levels and an increase in Bax and Bok levels in GCD II PCFs. Finally, GCD II PCFs are more susceptible to H(2)O(2)-induced cell death. Together, these results suggest that oxidative damage induced by decreased catalase is involved in GCD II pathogenesis, and antioxidant agents represent a possible treatment strategy
Files in This Item:
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DOI
10.2353/ajpath.2009.081001
Appears in Collections:
5. Research Institutes (연구소) > Corneal Dystrophy Research Institute (각막이상증연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
Yonsei Authors
Kim, Bong Yoon(김봉윤)
Kim, Eung Kweon(김응권) ORCID logo https://orcid.org/0000-0002-1453-8042
Kim, Tae Im(김태임) ORCID logo https://orcid.org/0000-0001-6414-3842
Ahn, So Yoen(안소연)
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
Cho, Hyun Ju(조현주)
Choi, Seung Il(최승일) ORCID logo https://orcid.org/0000-0001-7168-8795
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104064
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