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

Seung Il Choi, Tae-im Kim, Seo Kim Kyu, Bong Yoon Kim, So Yeon Ahn, Hyun Ju Cho, Keun Lee Hyung, Hyun Soo Cho, Eungkweon Kim

Research output: Contribution to journalArticle

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Abstract

Granular corneal dystrophy type II (GCD II) is an autosomal dominant disorder characterized by agedependent progressive accumulation of transforming growth factor-β-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-β-induced gene-h3. We also observed an increase in not only intracellular reactive oxygen species and H2O2 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 H2O2-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.

Original languageEnglish
Pages (from-to)248-261
Number of pages14
JournalAmerican Journal of Pathology
Volume175
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

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Catalase
Oxidative Stress
Fibroblasts
Transforming Growth Factors
Malondialdehyde
Reactive Oxygen Species
Cell Death
Antioxidants
Corneal Stroma
Corneal dystrophy Avellino type
Proteins
Glutathione Reductase
Glutathione Peroxidase
Superoxide Dismutase
Healthy Volunteers
Messenger RNA
Enzymes
Genes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

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title = "Decreased catalase expression and increased susceptibility to oxidative stress in primary cultured corneal fibroblasts from patients with granular corneal dystrophy type II",
abstract = "Granular corneal dystrophy type II (GCD II) is an autosomal dominant disorder characterized by agedependent progressive accumulation of transforming growth factor-β-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-β-induced gene-h3. We also observed an increase in not only intracellular reactive oxygen species and H2O2 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 H2O2-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.",
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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. / Choi, Seung Il; Kim, Tae-im; Kyu, Seo Kim; Kim, Bong Yoon; Ahn, So Yeon; Cho, Hyun Ju; Hyung, Keun Lee; Cho, Hyun Soo; Kim, Eungkweon.

In: American Journal of Pathology, Vol. 175, No. 1, 01.01.2009, p. 248-261.

Research output: Contribution to journalArticle

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AU - Choi, Seung Il

AU - Kim, Tae-im

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AU - Kim, Bong Yoon

AU - Ahn, So Yeon

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AU - Kim, Eungkweon

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AB - Granular corneal dystrophy type II (GCD II) is an autosomal dominant disorder characterized by agedependent progressive accumulation of transforming growth factor-β-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-β-induced gene-h3. We also observed an increase in not only intracellular reactive oxygen species and H2O2 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 H2O2-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.

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