Nuclear ferritin in corneal epithelial cells: tissue–specific nuclear transport and protection from UV–damage

Linsenmayer, Thomas F.; Cai, Cindy X.; Millholland, John M.; Beazley, Kelly E.; Fitch, John M.

doi:10.1016/j.preteyeres.2004.08.004

Cited by 35 publications

(22 citation statements)

References 57 publications

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“…55,56 Moreover, it seems that corneal epithelial cells have evolved a novel, nuclear ferritin-based mechanism for protecting their DNA against UV damage. 57 The corneal endothelium has also been shown to produce an autocrine factor against oxidative stress, vasoactive intestinal peptide, which may have some interest. 58 Finally, crystallins are abundant corneal proteins that display antioxidant properties.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of Ocular Anterior Chamber Tissues to Oxidative Damage and Its Relevance to the Pathogenesis of Glaucoma

Izzotti

Saccà

Longobardi

et al. 2009

Invest. Ophthalmol. Vis. Sci.

136

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Section: Discussionmentioning

confidence: 99%

Sensitivity of Ocular Anterior Chamber Tissues to Oxidative Damage and Its Relevance to the Pathogenesis of Glaucoma

Izzotti

Saccà

Longobardi

et al. 2009

Invest. Ophthalmol. Vis. Sci.

136

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“…Mechanical senescence, such as wing wear, has been found to reduce life expectancy in the honey bee (Neukirch, 1982), possibly because it induces an increased work load and, thereby, a higher metabolic rate (Neukirch, 1982;Cartar, 1992). UV light, moreover, constitutes a major environmental insult to all exposed tissues, including the visual system, and exposure can potentially damage a wide variety of macromolecular components, ranging from DNA to proteins and lipids, through the generation of ROS (Podhaisky et al, 2002;Parker et al, 2004;Linsenmayer et al, 2005). The lamina is vulnerable although chromophores are especially developed to absorb UV radiation (Miguel et al, 2002), and in humans oxidative stress-induced damage has been found to increase in retinal tissue with age (Parker et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Cellular senescence in honey bee brain is largely independent of chronological age

Seehuus

Krekling

Amdam

2006

Experimental Gerontology

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Accumulation of oxidative stress-induced damage in brain tissue plays an important role in the pathogenesis of normal aging and neurodegenerative diseases. Neuronal oxidative damage typically increases with age in humans, and also in the invertebrate and vertebrate model species most commonly used in aging research. By use of quantitative immunohistochemistry and Western blot, we show that this aspect of brain senescence is largely decoupled from chronological age in the honey bee (Apis mellifera). The bee is a eusocial insect characterized by the presence of a reproductive queen caste and a caste of functionally sterile female workers that performs various alloparental tasks such as nursing and foraging. We studied patterns of oxidative nitration and carbonylation damage in the brain of worker bees that performed nurse tasks as 8-and 200-day-olds and foraging tasks as 20-and 200-day-olds. In addition, we examined 180-day-old diutinus bees, a stress-resistant temporal worker form that survives unfavorable periods. Our results indicate that nitration damage occurs only at low levels in vivo, but that a 60-kDa protein from honey bee brain is selectively nitrated by peroxynitrite in vitro. Oxidative carbonylation is present at varying levels in the visual and chemosensory neuropiles of worker bees, and this inter-individual variation is better explained by social role than by chronological age.

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“…Nuclear ferritin is distributed nonrandomly, with preferential association with heterochromatin, which suggests that it might be involved in facilitating DNA synthesis (9,10). Ferritin in the nucleus has a protective function, as shown by its ability to protect DNA of corneal epithelial cells from UV damage and oxidative stress (11)(12)(13). Ferritin may also play a role in drug resistance mechanisms, as repeated exposure of cells to hydroxyurea results in an increased resistance to this toxic agent and an increase in ferritin mRNA (14).…”

Section: Introductionmentioning

confidence: 99%

Heavy Chain Ferritin siRNA Delivered by Cationic Liposomes Increases Sensitivity of Cancer Cells to Chemotherapeutic Agents

et al. 2011

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Approximately half of all gliomas are resistant to chemotherapy, and new therapeutic strategies are urgently needed to treat this cancer. We hypothesized that disrupting iron homeostasis in glioma cells could block tumor growth, based on an acute requirement for high levels of iron to meet energy requirements associated with their rapid growth. Ferritin is best known as an intracellular iron storage protein, but it also localizes to tumor cell nuclei where it seems to protect DNA from oxidative damage and to promote transcription. In this study, we hypothesize that silencing the H-ferritin (heavy chain ferritin) gene could increase tumor sensitivity to chemotoxins. To test this hypothesis, H-ferritin siRNA was delivered to several human cancer cell lines by using cationic liposomes (C-liposome). H-ferritin siRNA decreased protein expression by 80% within 48 hours, and this decrease was associated with more than 50% decrease in the LD 50 for DNA-alkylating agent carmustine (BCNU), which is commonly used to treat glioma in clinic. In a subcutaneous mouse model of human glioma, intratumoral injections of liposomes containing H-ferritin siRNA reduced the effective dose of BCNU needed for tumor suppression by more than 50%. A plasmid supercoil relaxation assay showed that H-ferritin specifically and directly protected DNA from BCNU treatment. H-ferritin siRNA additionally seemed to increase apoptosis in glioma cells in vitro upon H-ferritin knockdown. Overall, our results illustrate how silencing H-ferritin can effectively sensitize tumors to chemotherapy and also show the ability of C-liposomes to serve as a novel in vivo delivery tool for siRNAs. Cancer Res; 71(6); 2240-9. Ó2011 AACR.

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Nuclear ferritin in corneal epithelial cells: tissue–specific nuclear transport and protection from UV–damage

Cited by 35 publications

References 57 publications

Sensitivity of Ocular Anterior Chamber Tissues to Oxidative Damage and Its Relevance to the Pathogenesis of Glaucoma

Sensitivity of Ocular Anterior Chamber Tissues to Oxidative Damage and Its Relevance to the Pathogenesis of Glaucoma

Cellular senescence in honey bee brain is largely independent of chronological age

Heavy Chain Ferritin siRNA Delivered by Cationic Liposomes Increases Sensitivity of Cancer Cells to Chemotherapeutic Agents

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