Ferritin induction protects cortical astrocytes from heme-mediated oxidative injury

Regan, Raymond F.; Kumar, Nidhi; Fengtong, Gao; Guo, Yaping

doi:10.1016/s0306-4522(02)00243-9

Cited by 68 publications

(80 citation statements)

References 54 publications

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“…The ferritin H ARE comprises two copies of bidirectional AP1 motifs (68). Since (i) oxidative stress was shown to be involved in erythroid differentiation of K562 cells (18,47), (ii) hemin induces oxidative stress (54), and (iii) the human ferritin H ARE (at the Ϫ4.5kb region) is within the Ϫ5.2kb to Ϫ4.0kb region in which we identified a hemin-responsive element (Fig. 2a), we hypothesized that the hemin-responsive element is identical to the ARE.…”

Section: Resultsmentioning

confidence: 99%

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Hemin-Mediated Regulation of an Antioxidant-Responsive Element of the Human Ferritin H Gene and Role of Ref-1 during Erythroid Differentiation of K562 Cells

Iwasaki

Mackenzie

Hailemariam

et al. 2006

Molecular and Cellular Biology

101

108

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Section: Resultsmentioning

confidence: 99%

“…Increased ferritin content in the cells was shown to induce cytoprotection from oxidative damage (6,17,54). In addition, we and others demonstrated by overexpression that ferritin H is cytoprotective against oxidative stress in erythroleukemia cells (24) and other cell types (22,50,52).…”

mentioning

confidence: 89%

Hemin-Mediated Regulation of an Antioxidant-Responsive Element of the Human Ferritin H Gene and Role of Ref-1 during Erythroid Differentiation of K562 Cells

Iwasaki

Mackenzie

Hailemariam

et al. 2006

Molecular and Cellular Biology

101

108

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“…Conversely, the ferritin-bound storage iron is released when LIP is low in order to make iron available for cellular functions (26). This concept is supported by experimental evidence showing that the overexpression of H-ferritin reduces steady-state LIP levels and ensuing ROS production (14), whereas the inhibition of H-ferritin expression evokes an increase in the levels and pro-oxidant activity of LIP (27,28,44). Iron-regulated ferritin expression through the iron regulatory protein-iron-responsive element system has been well studied (40,54) and is believed to be a mechanism that controls LIP levels.…”

mentioning

confidence: 92%

“…Alternation of iron metabolism is part of the cellular response to TNF and is involved in TNF-induced cellular events such as NF-B activation (60). Ferritin expression is generally considered a means of protection against oxidative damage since the induction of ferritin by iron results in a resistance to various types of oxidative stimuli (2,44,50). H-ferritin-mediated resistance to TNF-induced apoptosis in HeLa and other cells has also been reported (12,41).…”

mentioning

confidence: 99%

Distinct Roles of Basal Steady-State and Induced H-Ferritin in Tumor Necrosis Factor-Induced Death in L929 Cells

Xie

Zhang

Zhou

et al. 2005

Molecular and Cellular Biology

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Tumor necrosis factor (TNF) alpha is a cytokine capable of inducing caspase-dependent (apoptotic) cell death in some cells and caspase-independent (necrosis-like) cell death in others. Here, using a mutagenesis screen for genes critical in TNF-induced death in L929 cells, we have found that H-ferritin deficiency is responsible for TNF resistance in a mutant line and that, upon treatment with TNF, this line fails to elevate levels of labile iron pool (LIP), critical for TNF-induced reactive oxygen species (ROS) production and ROS-dependent cell death. Since we found that TNF-induced LIP in L929 cells is primarily furnished by intracellular storage iron, the lesser induction of LIP in H-ferritin-deficient cells results from a reduction of intracellular iron storage caused by less H-ferritin. Different from some other cell lines, the H-ferritin gene in L929 cells is not TNF inducible; however, when H-ferritin is expressed in L929 cells under a TNF-inducible system, the TNF-induced LIP and subsequent ROS production and cell death were all prevented. Thus, LIP is a common denominator of ferritin both in the enhancement of cell death by basal steady-state H-ferritin and in protection against cell death by induced H-ferritin, thereby acting as a key determinant of TNF-induced cell death.

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“…This process is most efficient when Hb autoxidizes to methemoglobin (Balla et al, 1993), which occurs in intracranial hematomas (Bradley, 1993). Hemin, the oxidized form of heme, is a highly reactive compound that produces an iron-dependent injury to both neurons and astrocytes in cell culture and in vivo (Huang et al, 2002;Regan et al, 2002;Goldstein et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Astrocyte-specific heme oxygenase-1 hyperexpression attenuates heme-mediated oxidative injury

Benvenisti-Zarom

Regan

2007

Neurobiology of Disease

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In prior studies, we have observed that HO activity protects astrocytes from heme-mediated injury, but paradoxically increases neuronal injury. In this study, we tested the hypothesis that an adenovirus encoding the human HO-1 gene driven by an enhanced glial fibrillary acidic protein promoter (Ad-GFAP-HO-1) would increase HO-1 expression selectively in astrocytes, and provide cytoprotection. Treatment with 100 MOI Ad-GFAP-HO-1 for 24h resulted in HO-1 expression that was 6.4-fold higher in cultured primary astrocytes than in neurons. Astrocyte HO activity was increased by approximately fourfold over baseline, which was sufficient to reduce cell death after 24 h hemin exposure by 60%, as assessed by both MTT and LDH release assays. A similar reduction in cell protein oxidation, quantified by carbonyl assay, was also observed. These results suggest that HO-1 transgene expression regulated by an enhanced GFAP promoter selectively increases HO-1 expression in astrocytes, and is cytoprotective. Further investigation of this strategy in vivo is warranted.

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Ferritin induction protects cortical astrocytes from heme-mediated oxidative injury

Cited by 68 publications

References 54 publications

Hemin-Mediated Regulation of an Antioxidant-Responsive Element of the Human Ferritin H Gene and Role of Ref-1 during Erythroid Differentiation of K562 Cells

Hemin-Mediated Regulation of an Antioxidant-Responsive Element of the Human Ferritin H Gene and Role of Ref-1 during Erythroid Differentiation of K562 Cells

Distinct Roles of Basal Steady-State and Induced H-Ferritin in Tumor Necrosis Factor-Induced Death in L929 Cells

Astrocyte-specific heme oxygenase-1 hyperexpression attenuates heme-mediated oxidative injury

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