Ferritin and superoxide-dependent lipid peroxidation.

Thomas, Craig E.; Morehouse, Lee A.; Aust, Steven D.

doi:10.1016/s0021-9258(19)83617-7

Cited by 507 publications

(56 citation statements)

References 42 publications

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“…This is not unexpected, as increased iron levels in ulcer tissue have been reported earlier (Ackerman et al, 1988). Moreover, it is known that ROS and proteases are able to release iron from different iron-containing proteins (Thomas et al, 1985;Biemond et al, 1988;Fridovich, 1995) most probably enhancing the transfer of iron from the tissue into the exudate. Due to low available amounts of ulcer ¯uid, only total iron contents have been measured.…”

Section: Discussionsupporting

confidence: 61%

“…Venous hypertension results in enhanced erythrocyte extravasation into the interstitium through widened interendothelial pores (Wenner et al, 1980). Iron is released from hemoglobin of degraded erythrocytes, ferritin, hemosiderin (Thomas et al, 1985;Manuscript received August 21, 2000;revised January 10, 2001;accepted for publication February 1, 2001. Reprint requests to: Dr. Wolfgang Meyer-Ingold, Beiersdorf AG, Unnastrasse 48, D-20245 Hamburg, Germany. Email: karin.scharffetter@ uni-koeln.de Abbreviations: CDI, 1,1¢-carbonyldiimidazole; DFO, deferoxamine; LC/MS, liquid chromatography/mass spectrometry; MDA, malondialdehyde; MMP-1, matrix-degrading metalloproteinase 1.…”

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confidence: 99%

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Selective Pick-Up of Increased Iron by Deferoxamine-Coupled Cellulose Abrogates the Iron-Driven Induction of Matrix-Degrading Metalloproteinase 1 and Lipid Peroxidation in Human Dermal Fibroblasts In Vitro: A New Dressing Concept

Wenk¹,

Foitzik

Achterberg

et al. 2001

Journal of Investigative Dermatology

102

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Using atomic absorption spectrum analysis, we found iron levels in exudates from chronic wounds to be significantly increased (3.71 +/- 1.56 micromol per g protein) compared to wound fluids from acute wounds derived from blister fluids (1.15 +/- 0.62 micromol per g protein, p < 0.02), drainage fluids of acute wounds (0.87 +/- 0.34 micromol per g protein, p < 0.002), and pooled human plasma of 50 volunteers (0.42 micromol per g protein). Increased free iron and an increase in reactive oxygen species released from neutrophils represent pathogenic key steps that --via the Fenton reaction - are thought to be responsible for the persistent inflammation, increased connective tissue degradation, and lipid peroxidation contributing to the prooxidant hostile microenvironment of chronic venous leg ulcers. We herein designed a selective pick-up dressing for iron ions by covalently binding deferoxamine to cellulose. No leakage occurred following gamma sterilization of the dressing and, more importantly, the deferoxamine-coupled cellulose dressing retained its iron complexing properties sufficient to reduce iron levels found in chronic venous ulcers to levels comparable to those found in acute wounds. In order to study the functionality of the dressing, human dermal fibroblasts were exposed to a Fenton reaction mimicking combination of 220 microM Fe(III) citrate and 1 mM ascorbate resulting in a 4-fold induction of matrix-degrading metalloproteinase 1 as determined by a matrix-degrading metalloproteinase 1 specific enzyme-linked immunosorbent assay. This induction was completely suppressed by dissolved deferoxamine at a concentration of 220 microM or by an equimolar amount of deferoxamine immobilized to cellulose. In addition, the Fe(III) citrate and ascorbate driven Fenton reaction resulted in an 8-fold increase in malondialdehyde, the major product of lipid peroxidation, as determined by high pressure liquid chromatography. This increase in malondialdehyde levels could be significantly reduced in the presence of the selective pick-up dressing coupled with deferoxamine suggesting that the deferoxamine dressing, in fact, prevents the development of a damaging prooxidant microenvironment and also protects from unfavorable consequences like matrix-degrading metalloproteinase 1 and lipid peroxide induction.

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Section: Discussionsupporting

confidence: 61%

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confidence: 99%

Selective Pick-Up of Increased Iron by Deferoxamine-Coupled Cellulose Abrogates the Iron-Driven Induction of Matrix-Degrading Metalloproteinase 1 and Lipid Peroxidation in Human Dermal Fibroblasts In Vitro: A New Dressing Concept

Wenk¹,

Foitzik

Achterberg

et al. 2001

Journal of Investigative Dermatology

102

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“…Tissue ferritin stores have been shown to be markedly increased in iron overload diseases (Zuyderhoudt et al, 1983). Ferritin is a potential source of iron for oxidative damage (Thomas et al, 1985;Reif, 1992), and if the regulation of iron within ferritin in the wound environment was disrupted and the ferritin iron was mobilized, this could contribute to free-radical-induced cell damage.…”

Section: Discussionmentioning

confidence: 99%

Iron and 8-Isoprostane Levels in Acute and Chronic Wounds

Yeoh-Ellerton

Stacey

2003

Journal of Investigative Dermatology

101

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The purpose of this study was to determine differences in iron and iron protein (ferritin and transferrin) levels in chronic venous ulcers and acute wounds. The deleterious effect of iron in free-radical-induced tissue damage was indirectly examined by assessing 8-isoprostane levels and antioxidant status in wound fluid samples. Wound fluid samples from chronic leg ulcers in nonhealing and healing phases and wound fluid from mastectomy wounds were assayed for ferritin, transferrin, total iron, 8-isoprostane, and total antioxidant status. Immunohistochemistry and Perls' staining were performed on paired biopsies from chronic leg ulcers and on normal skin biopsies. Chronic wound fluid had significantly greater levels of ferritin (p < 0.05) and lower levels of transferrin (p < 0.001) than acute wound fluid and there was a significant reduction in the level of ferritin in healing compared to nonhealing chronic leg ulcers (p < 0.05). No significant differences were observed in the levels of total iron present in the wound fluids. Histologic staining showed consistently more ferritin and ferric iron in chronic wound tissue than in normal skin. Elevated levels of 8-isoprostane and antioxidants were observed for chronic wound fluid compared to acute wound fluid (p < 0.001). These results suggest the existence of an environment of oxidative stress in chronic wounds and the likely contribution of iron to exacerbating tissue damage and delaying healing in these wounds.

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“…Under the action of certain reductants, including superoxide (the major species of ROS), ferritin-bound Fe 3+ can be reduced to Fe 2+ and subsequently released from ferritin [ 20 – 22 ]. Then accumulated redox-active iron could redox cycle to produce a Fenton reaction and peroxidize lipids as well as the further disintegration of ferritin [ 21 ], promoting cell ferroptosis [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Berberine alleviates liver fibrosis through inducing ferrous redox to activate ROS-mediated hepatic stellate cells ferroptosis

Tan

et al. 2021

Cell Death Discov.

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Berberine (BBR) has been explored as a potential anti-liver fibrosis agent, but the underlying mechanisms are unknown. In the current study, we aimed to investigate the molecular mechanisms underlying the effect of BBR against liver fibrogenesis in thioacetamide (TAA) and carbon tetrachloride (CCl4) induced mouse liver fibrosis. In addition to i.p. injection with TAA or CCl4, mice in the treatment group received BBR intragastrically. Concurrently, combined with TAA and BBR treatment, mice in the inhibitor group were injected i.p. with ferrostatin-1 (Fer-1). Hepatic stellate cells (HSCs) were also used in the study. Our results showed that BBR obviously alleviated mouse liver fibrosis and restored mouse liver function; however, the pharmacological effects of BBR against liver fibrosis were significantly diminished by Fer-1 treatment. Mechanically, BBR impaired the autophagy–lysosome pathway (ALP) and increased cell reactive oxygen species (ROS) production in HSCs. ROS accelerated the breakdown of the iron-storage protein ferritin and sped up iron release from ferritin, which resulted in redox-active iron accumulation in HSCs. Lipid peroxidation and glutathione (GSH) depletion triggered by the Fenton reaction promoted ferroptosis and attenuated liver fibrosis. Furthermore, impaired autophagy enhanced BBR-mediated ferritin proteolysis to increase cellular ferrous overload via the ubiquitin–proteasome pathway (UPS) in HSCs and triggered HSC ferroptosis. Collectively, BBR alleviated liver fibrosis by inducing ferrous redox to activate ROS-mediated HSC ferroptosis. Our findings may be exploited clinically to provide a potential novel therapeutic strategy for liver fibrosis.

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Ferritin and superoxide-dependent lipid peroxidation.

Cited by 507 publications

References 42 publications

Selective Pick-Up of Increased Iron by Deferoxamine-Coupled Cellulose Abrogates the Iron-Driven Induction of Matrix-Degrading Metalloproteinase 1 and Lipid Peroxidation in Human Dermal Fibroblasts In Vitro: A New Dressing Concept

Selective Pick-Up of Increased Iron by Deferoxamine-Coupled Cellulose Abrogates the Iron-Driven Induction of Matrix-Degrading Metalloproteinase 1 and Lipid Peroxidation in Human Dermal Fibroblasts In Vitro: A New Dressing Concept

Iron and 8-Isoprostane Levels in Acute and Chronic Wounds

Berberine alleviates liver fibrosis through inducing ferrous redox to activate ROS-mediated hepatic stellate cells ferroptosis

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