Iron release analyses from ferritin by visible light irradiation

Ohishi, Kentaro; Zhang, Xiao Mei; Moriwaki, Shinichi; Hiramitsu, Tadahisa; Matsugo, Seiichi

doi:10.1080/10715760500177807

Cited by 12 publications

(12 citation statements)

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“…This Fenton-catalyzed oxidative stress is believed to trigger biochemical cascades that lead to progressive degeneration [51], [52]. This hypothesis has been indirectly confirmed by the effectiveness of the metal chelator, deferiprone, to reduce iron overload-induced retinal damage in a transgenic mouse model [53] and desferrioxamine's ability to protect against light-induced retinal damage [17], presumably by chelating iron released from ferritin by light [7]. Therefore, it was hypothesized that multi-functional antioxidants 4 and 8 should be neuroprotective in a rat model of light-induced retinal damage.…”

Section: Discussionmentioning

confidence: 93%

“…In the rat, light-induced retinal degeneration mimics changes associated with late-stage, atrophic retinal degeneration that include RPE ablation and photoreceptor cell death [6]. Although the exact mechanism(s) of light-induced photoreceptor damage have not been established, continuous visible irradiation has been suggested to generate superoxide and promote iron release from ferritin [7], [8], [9]. Together, the free iron and superoxide anions can undergo the Haber-Weiss and Fenton reactions to generate damaging hydroxyl radicals [10], that lead to lipid peroxidation of retinal tissues [11], [12], [13] and plasma membrane injury [12], [14], [15], [16].…”

Section: Introductionmentioning

confidence: 99%

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Orally Active Multi-Functional Antioxidants Are Neuroprotective in a Rat Model of Light-Induced Retinal Damage

et al. 2011

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BackgroundProgression of age-related macular degeneration has been linked to iron dysregulation and oxidative stress that induce apoptosis of neural retinal cells. Since both antioxidants and chelating agents have been reported to reduce the progression of retinal lesions associated with AMD in experimental animals, the present study evaluates the ability of multi-functional antioxidants containing functional groups that can independently chelate redox metals and quench free radicals to protect the retina against light-induced retinal degeneration, a rat model of dry atrophic AMD.Methods/ResultsProof of concept studies were conducted to evaluate the ability of 4-(5-hydroxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8) to reduce retinal damage in 2-week dark adapted Wistar rats exposed to 1000 lx of light for 3 hours. Assessment of the oxidative stress markers 4- hydroxynonenal and nitrotyrosine modified proteins and Thioredoxin by ELISA and Western blots indicated that these compounds reduced the oxidative insult caused by light exposure. The beneficial antioxidant effects of these compounds in providing significant functional and structural protection were confirmed by electroretinography and quantitative histology of the retina.Conclusions/SignificanceThe present study suggests that multi-functional compounds may be effective candidates for preventive therapy of AMD.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Orally Active Multi-Functional Antioxidants Are Neuroprotective in a Rat Model of Light-Induced Retinal Damage

et al. 2011

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“…The free radical mechanism requires a transition metal catalyst (typically Fe +2 or Cu +2 ). One biologically significant form of iron is ferritin, which has been shown to enhance lipid peroxidation in photoreceptor outer segment (POS) membranes in the presence of light (18,19), and also is relatively abundant in the retina (20,21). Hence, we suspect that ferritin may be implicated in the formation of 7KCh in the retina.…”

Section: Introductionmentioning

confidence: 99%

Photodamage Generates 7‐keto‐ and 7‐hydroxycholesterol in the Rat Retina via a Free Radical‐mediated Mechanism

Rodríguez

Fliesler

2009

Photochem & Photobiology

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Albino Sprague–Dawley rats are known to undergo photoreceptor degeneration after exposure to constant light, but the molecular mechanism(s) by which the photoreceptors degenerate is not fully understood. We hypothesized that cytotoxic oxysterols are generated in situ in the retina under such conditions and may be involved in the degenerative mechanism. Thus, photodamaged and control rat retinas were analyzed for oxysterols by liquid chromatography mass spectroscopy. Elevated levels of two known cytotoxic oxysterols, 7-ketocholesterol (7KCh) and 7αβ-hydroxycholesterol (7HCh), were found in the photodamaged retinas, at levels six-fold and 50-fold greater, respectively, than those found in non photodamaged controls. Notably, two key intermediates, 5,6α,β-epoxycholesterol (5,6-epoxyCh) and 7αβ-hydroperoxy-cholesterol, were also identified, indicating that the formation of 7KCh and 7HCh is mediated by a free radical mechanism. By immunohistochemistry, 7KCh was localized to the ganglion cell layer, photoreceptor inner segments and retinal pigment epithelium (RPE), which coincides with the localization of ferritin in the retina. Exposure of a mixture of ferritin and low-density lipoprotein to intense white light in vitro produced similar oxysterol species as seen in vivo. We propose that the increased levels of 7KCh and 7HCh, especially in photoreceptor inner segments and RPE, may arise due to ferritin-catalyzed reactions and may be important contributors to the photoreceptor degeneration observed in photodamaged rats.

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“…Ferritin (heavy and light chains) localizes to the mitochondria and is abundant in the retina ( 49,50 ). But most importantly, ferritin is known to release its iron when exposed to bright visible light ( 51 ). Ferritin in the presence of light can induce lipid peroxidation in purifi ed photoreceptor outer segments ( 52 ) and in LDL ( 10 ).…”

Section: +2mentioning

confidence: 99%

Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration

Rodríguez

Larráyoz

2010

Journal of Lipid Research

121

115

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Journal of Lipid Research Volume 51, 20102847 their actions affect the retina and the retinal pigment epithelium (RPE) ( 8-10 ). One particular oxysterol, 7-ketocholesterol (7KCh), has been found more abundantly than other oxysterols in the retina ( 9, 10 ). This oxysterol is known to have potent pharmacological properties that lead to infl ammation and cell death in a variety of cell types ( 1-10 ). This review will focus on what is known about this molecule and the potential implications of its presence in the retina. The retina is a light-capturing tissue that contains at least 5 cell classes and more than 50 different cell types, each performing unique functions that ultimately provide the visual centers in the brain the information to achieve image formation and visual perception. The retina faces a unique photooxidative environment that generates challenges not encountered by other neurological tissues or organs. Phototransduction requires the retina to have a high metabolic rate ( 11 ) and multiple and complex membrane structures ( 12 ). The photoreceptor outer segments are enriched in the highly photosensitive docosahexaenoic acid and other Abstract This review will discuss the formation and potential implications of 7-ketocholesterol (7KCh) in the retina. 7KCh is a proinfl ammatory oxysterol known to be present in high amounts in oxidized LDL deposits associated with atheromatous plaques. 7KCh is generated in situ in these lipoprotein deposits where it can accumulate and reach very high concentrations. In normal primate retina, 7KCh has been found associated with lipoprotein deposits in the choriocapillaris, Bruch's membrane, and the retinal pigment epithelium (RPE). In photodamaged rats, 7KCh has been found in the neural retina in areas of high mitochondrial content, ganglion cells, photoreceptor inner segments and synapses, and the RPE. Intermediates found by LCMS indicate 7KCh is formed via a free radical-mediated mechanism catalyzed by iron. 7KCh seems to activate several kinase signaling pathways that work via nuclear factor B and cause the induction of vascular endothelial growth factor, interleukin (IL)-6, and IL-8. There seems to be little evidence of 7KCh metabolism in the retina, although some form of effl ux mechanism may be active. The chronic mode of formation and the potent infl ammatory properties of 7KCh indicate it may be an "age-related" risk factor in aging diseases such as atherosclerosis, Alzheimer's, and age-related macular degeneration. -Rodríguez, I. R., and I. M. Larrayoz. Cholesterol oxidation in the retina: implications of 7-KCh formation in chronic infl ammation and age-related macular degeneration. J. Lipid Res . 2010. 51: 2847-2862. Supplementary key words 7-ketocholesterol • cytokines • oxysterolsIn the past year, numerous reviews have been published that extensively discuss the multiple functions of oxysterols and their complex relationships to diseases ( 1-7 ). However, the formation and function of oxysterols in the retina has not been well studied. Emerging studies are...

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Iron release analyses from ferritin by visible light irradiation

Cited by 12 publications

References 14 publications

Orally Active Multi-Functional Antioxidants Are Neuroprotective in a Rat Model of Light-Induced Retinal Damage

Orally Active Multi-Functional Antioxidants Are Neuroprotective in a Rat Model of Light-Induced Retinal Damage

Photodamage Generates 7‐keto‐ and 7‐hydroxycholesterol in the Rat Retina via a Free Radical‐mediated Mechanism

Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration

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