Protection from Oxidative Insult in Glutathione Depleted Lens Epithelial Cells

Reddan, John R.; Giblin, Frank J.; Kadry, Razan; Leverenz, Victor R.; Pena, John; Dziedzic, Dorothy C.

doi:10.1006/exer.1998.0606

Cited by 38 publications

(24 citation statements)

References 38 publications

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“…In agreement with previous reports, the ninein antibodies were found to label the centrosome in all cell types studied, including UE-1 (Lawlor et al, 1999), PtK2, MDCKII, Caco2, FHL124 (Reddan et al, 1999), hTERT RPE (Rambhatla et al, 2002) and ARPE-19 (Dunn et al, 1996;Bouckson-Castaing et al, 1996;Mogensen et al, 2000;Piel et al, 2000) (Fig. 2A).…”

Section: Resultssupporting

confidence: 91%

Ninein is released from the centrosome and moves bi-directionally along microtubules

Moss

Bellett

Carter

et al. 2007

Journal of Cell Science

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Cell-to-cell contact and polarisation of epithelial cells involve a major reorganisation of the microtubules and centrosomal components. The radial microtubule organisation is lost and an apico-basal array develops that is no longer anchored at the centrosome. This involves not only the relocation of microtubules but also of centrosomal anchoring proteins to apical non-centrosomal sites. The relocation of microtubule minus-end-anchoring proteins such as ninein to the apical sites is likely to be essential for the assembly and stabilisation of the apico-basal arrays in polarised epithelial cells. In this study, we establish that ninein is highly dynamic and that, in epithelial cells, it is present not only at the centrosome but also in the cytoplasm as distinct speckles. Live-cell imaging reveals that GFP-ninein speckles are released from the centrosome and move in a microtubule-dependent manner within the cytoplasm and thus establishes that epithelial cells possess the mechanical means for relocation of ninein to non-centrosomal anchoring sites. We also provide evidence for the deployment of ninein speckles to apical anchoring sites during epithelial differentiation in both an in situ tissue and an in vitro culture system. In addition, the findings suggest that the non-centrosomal microtubule anchoring sites associate with adherens junctions in polarised epithelial cells

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Section: Resultssupporting

confidence: 91%

Ninein is released from the centrosome and moves bi-directionally along microtubules

Moss

Bellett

Carter

et al. 2007

Journal of Cell Science

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“…In an early attempt to determine the mechanism by which ROS lead to cataract formation, it was found that Tempol prevented the H 2 O 2 -induced inhibition of cell growth, membrane blebbing, decreases in DNA-repair protein activation, and limited the amount of DNA damage [89]. It was later shown that Tempol also protected cultured glutathione-depleted lens epithelial cells from H 2 O 2 toxicity [90]. As GSH-depletion is known to exist in most forms of cataract, it is argued that Tempol may prevent or slow the progression of this condition.…”

Section: Ocular Damagementioning

confidence: 99%

The chemistry and biology of nitroxide compounds

Soule

Hyodo

Matsumoto

et al. 2007

Free Radical Biology and Medicine

459

387

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Cyclic nitroxides are a diverse range of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15-20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications. Biologically relevant effects of nitroxides have been described including their ability to degrade superoxide and peroxide, inhibit Fenton reactions and undergo radical-radical recombination. Cellular studies defined the activity of nitroxides in vitro. By modifying oxidative stress and altering the redox status of tissues, nitroxides have been found to interact with and alter many metabolic processes. These interactions can be exploited for therapeutic and research use including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. While much remains to be done, many applications have been well studied and some are presently being tested in clinical trials. The therapeutic and research uses of nitroxide compounds are reviewed here with a focus on the progress from initial development to modern trials.

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“…Of particular interest for understanding the interplay of GSH and hydrogen peroxide in the presence of metals, has been a recent study on lens epithelial cells [95]. Cells were found to become more sensitive to H 2 O 2 if GSH was depleted; however, cytotoxicity was only evident if iron was redox active.…”

Section: A Theory For Human Nuclear Cataractmentioning

confidence: 99%

Age-Related Nuclear Cataract: A Lens Transport Problem

2000

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Age-related nuclear cataract is a major cause of blindness. It is characterised by opacification and colouration in the centre of the lens and is accompanied by extensive protein oxidation. The reason for the onset of nuclear cataract is not known, but it is proposed here that the underlying cause is the development, with age, of a barrier to the transport of metabolites within the lens. Such a barrier may result in an increase in the half-lives of reactive molecules, such as UV filters, thus promoting posttranslational modification of proteins in the nucleus and may also act to prevent an adequate flux of antioxidants from reaching the lens interior and, as a consequence, allow oxidation of nuclear components. Further, this oxidation may take place even if the lens outer cortex and epithelium remain perfectly functional.

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Protection from Oxidative Insult in Glutathione Depleted Lens Epithelial Cells

Cited by 38 publications

References 38 publications

Ninein is released from the centrosome and moves bi-directionally along microtubules

Ninein is released from the centrosome and moves bi-directionally along microtubules

The chemistry and biology of nitroxide compounds

Age-Related Nuclear Cataract: A Lens Transport Problem

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