Age-related cataracts and Prdx6: correlation between severity of lens opacity, age and the level of Prdx 6 expression

Hasanova, Nailya; Kubo, Eri; Kumamoto, Yuko; Takamura, Yoshihiro; Akagi, Yoshio

doi:10.1136/bjo.2008.152272

Cited by 21 publications

(14 citation statements)

References 24 publications

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“…In the cornea, a role for peroxiredoxin VI has previously been demonstrated in wound healing (Pak et al 2006;Tchah et al 2005). In the human intraocular lens, the expression of peroxiredoxin III and VI has previously been shown in lens epithelium and stroma, and an increase in expression levels in cataract specimens has been well established, suggesting a role for these enzymes in protection from oxidative stress (Hasanova et al 2009;Kubo et al 2008;Moreira et al 2008).…”

Section: Discussionmentioning

confidence: 98%

Peroxiredoxin I and II in Human Eyes

Klebe

Callahan

Power

2013

J Histochem Cytochem.

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SummaryPeroxiredoxin I and II are both 2-Cys members of the peroxiredoxin family of antioxidant enzymes and inactivate hydrogen peroxide. On western blotting, both enzymes appeared as 22-kD proteins and were present in the sclera, retina and iris. Immunohistochemistry showed strong cytoplasmic labeling in the basal cells of the corneal epithelial layer and the corneoscleral limbus. The melanocytes within the stroma of the iris and the anterior epithelial cells of the lens also showed strong cytoplasmic labeling. The fibrous structure of the stroma and the posterior surface of the ciliary body were also labeled. There was also strong labeling for both enzymes in the photoreceptors and the inner and outer plexiform layers of the retina. There was increased labeling of peroxiredoxin I and II in pterygium. In normal conjunctiva and cornea, only the basal cell layer showed labeling for peroxiredoxin I and II, whereas, in pterygia, there was strong cytoplasmic labeling in most cells involving the full thickness of the epithelium. Co-localization of the DNA oxidation product 8-hydroxy-2'-deoxyguanosine antibody with the nuclear dye 4',6'-diamidino-2-phenylindole dihydrochloride indicated that the majority of the oxidative damage was cytoplasmic; this suggested that the mitochondrial DNA was most affected by the UV radiation in this condition. (J Histochem Cytochem 62:85-96, 2014)

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Section: Discussionmentioning

confidence: 98%

Peroxiredoxin I and II in Human Eyes

Klebe

Callahan

Power

2013

J Histochem Cytochem.

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“…In addition, the expression of Prdx6 mRNA was significantly lower in lenses with relatively more severe nuclear and cortical cataracts in patients aged ≤70 years [47]. Based on the results of this study, we speculated that the decreased expression of Prdx6 mRNA may induce oxidative stress in human lenses, leading in turn to age-related cataracts.…”

Section: Introductionmentioning

confidence: 86%

“…We previously reported an association between Prdx6 expression in human cataractous lenses and age: older patients (aged >70 years) showed significantly lower expression of Prdx6 mRNA than did relatively younger patients (aged ≤70 years) [47]. In addition, the expression of Prdx6 mRNA was significantly lower in lenses with relatively more severe nuclear and cortical cataracts in patients aged ≤70 years [47].…”

Section: Introductionmentioning

confidence: 99%

The role of Prdx6 in the protection of cells of the crystalline lens from oxidative stress induced by UV exposure

Shibata

et al. 2016

Jpn J Ophthalmol

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Purpose The immediate aim of this study was to investigate alterations in peroxiredoxin (Prdx) 6 at posttranslational levels, and the levels of protein oxidation, lipid peroxidation, and reactive oxygen species (ROS) in lens epithelial cells (LECs) after exposure to severe oxidative stress, such as ultraviolet-B (UV-B). Our ultimate aim was to provide new information on antioxidant defenses in the lens and their regulation, thereby broadening existing knowledge of the role of Prdx6 in lens physiology and pathophysiology. Methods The expression of the hyperoxidized form of Prdx6 and oxidation of protein were analyzed by western blotting and the OxyBlot assay in human LECs (hLECs). ROS levels were quantified using DCFH-DA dye, and cell viability was quantified by the MTS and TUNEL assays. To evaluate the protective effect of Prdx6, we cultured lenses with or without the TAT transduction domain (TAT-HA-Prdx6) and observed (and photographed) the cultures at specified time-points after the exposure to UV-B for the development of opacity. Results Prdx6 in hLECs was hyperoxidized after exposure to high amounts of UV-B. UV-B treatment of hLECs increased the levels of cell death, protein oxidation, and ROS. hLECs exposed to UV-B showed higher levels of ROS, which could be reduced by the application of extrinsic TAT-HA-Prdx6, attenuating UV-B-induced lens opacity and apoptotic cell death. Conclusion Excessive oxidative stress induces the hyperoxidation of Prdx6 and may reduce the ability of Prdx6 to protect LECs against ROS or stresses. Because extrinsic Prdx6 could attenuate UV-B-induced abuse, this molecule may have a potential in preventing cataractogenesis.

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“…Lower Prdx6 expression correlated with a younger age for human cataract surgery while treatment with Prdx6 delayed cataract formation in animal models (157)(158)(159) and protected against cytotoxicity in retinal pericytes (137). Prdx6 content in blood was increased significantly with experimental human hypobaric hypoxia as a model for acute mountain sickness (160).…”

Section: Other Pathophysiologymentioning

confidence: 97%

The phospholipase A2 activity of peroxiredoxin 6 [S]

Fisher

2018

Journal of Lipid Research

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Peroxiredoxin 6 (Prdx6) is a Ca 2+ -independent intracellular phospholipase A 2 (called aiPLA 2 )that is localized to cytosol, lysosomes, and lysosomal-related organelles. Activity is minimal at cytosolic pH but is increased significantly with enzyme phosphorylation, at acidic pH, and in the presence of oxidized phospholipid substrate; maximal activity with phosphorylated aiPLA 2 is ~2 µmol/min/mg protein. Prdx6 is a "moonlighting" protein that also expresses glutathione peroxidase and lysophosphatidylcholine acyl transferase activities.The catalytic site for aiPLA 2 activity is an S32-H26-D140 triad; S32-H26 is also the phospholipid binding site. Activity is inhibited by a serine "protease" inhibitor (diethyl p-nitrophenyl phosphate),an analogue of the PLA 2 transition state (1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol, MJ33), and by two naturally occurring proteins (surfactant protein A and p67 phox ), but not by bromoenol lactone. aiPLA 2 activity has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase (NOX2). The enzyme has been implicated in acute lung injury, carcinogenesis, neurodegenerative diseases, diabetes, male infertility, and sundry other conditions although its specific roles have not been well defined. Protein mutations and animal models are now available to further investigate the roles of Prdx6-aiPLA 2 activity in normal and pathological physiology.

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Age-related cataracts and Prdx6: correlation between severity of lens opacity, age and the level of Prdx 6 expression

Abstract: These findings suggest that oxidative stress contributes to nuclear cataract formation and that a local decrease in Prdx6 in cataractous lenses may indicate the initiation of age-related cataract formation.

Cited by 21 publications

References 24 publications

Peroxiredoxin I and II in Human Eyes

Peroxiredoxin I and II in Human Eyes

The role of Prdx6 in the protection of cells of the crystalline lens from oxidative stress induced by UV exposure

The phospholipase A2 activity of peroxiredoxin 6 [S]

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