The Effect of Photochemical Stress Upon the Lenses of Normal and Glutathione Peroxidase-1 Knockout Mice

Spector, Abraham; Kuszak, J.R.; Ma, Wu; Wang, Ren-Rong; Ho, Ye-Shih; Yang, Yanling

doi:10.1006/exer.1998.0548

Cited by 33 publications

(30 citation statements)

References 31 publications

(48 reference statements)

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“…76 Briefly, cells were cultured in 75 mm tissue culture flasks in a 5% CO2 environment at 371C following standard procedures. Cells were trypsinized (0.25%) and plated in culture dishes at a density of 5 Â 10 5 in 60 mm plates or 1 Â 10 6 in 100 mm plates when required.…”

Section: Lecs and Lens Organ Culturementioning

confidence: 99%

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Impaired homeostasis and phenotypic abnormalities in Prdx6−/−mice lens epithelial cells by reactive oxygen species: increased expression and activation of TGFβ

et al. 2005

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PRDX6, a member of the peroxiredoxins (PRDXs) family, is a key player in the removal of reactive oxygen species (ROS). Using targeted inactivation of the Prdx6 gene, we present evidence that the corresponding protein offsets the deleterious effects of ROS on lens epithelial cells (LECs) and regulates gene expression by limiting its levels. PRDX6-depleted LECs displayed phenotypic alterations and elevated a-smooth muscle actin and big-h3 expression (markers for cataractogenesis), indistinguishable from transforming growth factor b (TGFb)-induced changes. Biochemical assays disclosed enhanced levels of ROS, as well as high expression and activation of TGFb1 in Prdx6 À/À LECs. A CAT assay revealed transcriptional repression of lens epithelium-derived growth factor (LEDGF), HSP27, and aB-crystallin promoter activities in these cells. A gel mobility shift assay demonstrated the attenuation of LEDGF binding to heat shock or stress response elements present in these genes. A supply of PRDX6 toPrdx6 À/À LECs reversed these changes. Based on the above data, we propose a rheostat role for PRDX6 in regulating gene expression by controlling the ROS level to maintain cellular homeostasis.

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Section: Lecs and Lens Organ Culturementioning

confidence: 99%

“…76 Lenses were photographed using a slit lamp and dissection microscope, following H 2 O 2 exposure. For histopathological evaluation, lenses from both groups of mice were fixed in 4% paraformaldehyde in 20 mM phosphate-buffered saline, pH 7.4, embedded in paraffin, and cut into 5 mm sections.…”

Section: Lecs and Lens Organ Culturementioning

confidence: 99%

Impaired homeostasis and phenotypic abnormalities in Prdx6−/−mice lens epithelial cells by reactive oxygen species: increased expression and activation of TGFβ

et al. 2005

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“…However, the mice were offspring of four KO and two WT mating pairs formed from progeny of a mice for Sod1, the gene coding for Cu/Zn-SOD, show increased vulnerability to noise relative to wild types single heterozygous mating pair, so that the contributions of genetic modifiers were randomized. Addi- (Ohlemiller et al 1999a;McFadden et al 2000) and increased cochlear degeneration with age (McFadden tional details and procedures for genotyping of parentals are given elsewhere (Ho et al ). et al 1999aMcFadden et al 1999b;McFadden et al 2000).…”

Section: Animalsmentioning

confidence: 99%

“…Addi- (Ohlemiller et al 1999a;McFadden et al 2000) and increased cochlear degeneration with age (McFadden tional details and procedures for genotyping of parentals are given elsewhere (Ho et al ). et al 1999aMcFadden et al 1999b;McFadden et al 2000). The impact of SOD deficiency in young adult mice (1-3 months old) was modest, yet an early and…”

Section: Animalsmentioning

confidence: 99%

“…Studies employing this strategy with enzymes superoxide dismuthis work has appeared previously (Ohlemiller et al 2000a). tase (SOD) and glutathione peroxidase (GPx) have provided strong support for a relationship between antioxidant status and susceptibility to tissue injury (Reaume et al 1996;Kondo et al 1997; Yoshida et al 1997;Schwartz et al 1998;Spector et al 1998;Fu et al 1999;Jaeschke et al 1999;Klivenyi et al 2000).…”

Section: Introductionmentioning

confidence: 99%

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