Distinct regulatory mechanisms of the human ferritin gene by hypoxia and hypoxia mimetic cobalt chloride at the transcriptional and post-transcriptional levels

Huang, Bowen; Miyazawa, Masaki; Tsuji, Yoshiaki

doi:10.1016/j.cellsig.2014.08.018

Cited by 40 publications

(23 citation statements)

References 51 publications

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Section: Discussionsupporting

confidence: 83%

“…This indicates that the targets of increased cobalt chloride and decreased oxygen (probably through the generation of reactive oxygen species; Bell et al 2007) are separable. These results align with previous findings that have demonstrated differential effects brought about by cobalt chloride and hypoxia treatments (Vengellur et al 2005;Huang et al 2014a).Precisely how either insult affects BLMP-1 to alter transcriptional output in C. elegans will require more investigation; however, it is intriguing to note that hypoxia-initiated and BLMP-1-dependent increases in histone acetylation at the F45D3.4 promoter may point to a shared response pathway that includes the prolongevity factor LIN-40, one of the other two positive hits identified in our screen. LIN-40 is an essential component of the nucleosome remodeling deacetylase (NuRD) complex (Johnsen and Baillie 1991;Solari et al 1999) that was recently shown to promote stress resistance and longevity in a circuit that involves the germline and the insulin pathway (Zimmerman and Kim 2014).…”

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confidence: 83%

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A HIF-Independent Mediator of Transcriptional Responses to Oxygen Deprivation in Caenorhabditis elegans

et al. 2014

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The adaptive response to hypoxia is accompanied by widespread transcriptional changes that allow for prolonged survival in low oxygen. Many of these changes are directly regulated by the conserved hypoxia-inducible factor-1 (HIF-1) complex; however, even in its absence, many oxygen-sensitive transcripts in Caenorhabditis elegans are appropriately regulated in hypoxia. To identify mediators of these non-HIF-dependent responses, we established a hif-1 mutant reporter line that expresses GFP in hypoxia or when worms are treated with the hypoxia mimetic cobalt chloride (CoCl 2 ). The reporter is selective and HIF independent, in that it remains insensitive to a number of cellular stresses, but is unaffected by mutation of the prolyl hydroxylase egl-9, suggesting that the regulators of this response pathway are different from those controlling the HIF pathway. We used the HIF-independent reporter to screen a transcription factor RNA interference (RNAi) library and identified genes that are required for hypoxia-sensitive and CoCl 2 -induced GFP expression. We identified the zinc finger protein BLMP-1 as a mediator of the HIF-independent response. We show that mutation of blmp-1 renders animals sensitive to hypoxic exposure and that blmp-1 is required for appropriate hypoxic-induced expression of HIF-independent transcripts. Further, we demonstrate that BLMP-1 is necessary for an increase of hypoxia-dependent histone acetylation within the promoter of a non-HIF-dependent hypoxia response gene.KEYWORDS hypoxia; HIF independent; BLMP-1; C. elegans C ELLS are routinely challenged with low-oxygen conditions that drive compensatory responses. For instance, in development, low-oxygen conditions induce differentiation of placental cells (Dunwoodie 2009), and in diseased states, hypoxia is often a major contributing factor in cardiovascular disease and in the progression of solid tumor growth (Denko 2008;Semenza 2014). These low-oxygen challenges, whether scripted as in development or as consequences of physiologic dysfunction, are confronted by rapid cellular changes and by slower responses such as those mediated by the hypoxiainducible factor-1 (HIF-1) transcription pathway.The conserved HIF-1 complex regulates the expression of a broad set of genes that affect various aspects of metabolism, vascularization, and cell survival across species (Semenza 2011). In normoxia, the HIF-1 pathway is rendered inactive by prolyl hydroxylases (PHDs) that use molecular oxygen to modify conserved proline residues on the HIF-1a subunit of the transcription factor. The proline-hydroxylated HIF-1a is recognized by the von Hippel-Lindau (VHL) tumor suppressor protein, which targets HIF-1a for degradation (Bruick and McKnight 2001;Epstein et al. 2001). In hypoxia, owing to the reduced activity of PHD, unmodified HIF-1a pairs with the oxygen insensitive HIF-1b and the complex is transcriptionally active (Berra et al. 2006).The nematode Caenorhabditis elegans is adept at enduring periods of low oxygen (Powell-Coffman 2010). Not surprisin...

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Section: Discussionsupporting

confidence: 83%

supporting

confidence: 83%

A HIF-Independent Mediator of Transcriptional Responses to Oxygen Deprivation in Caenorhabditis elegans

et al. 2014

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“…Similar effects have been seen in macrophages, where INF-γ activated U937 cells treated with TNF-α also induced FTH mRNA expression (7). Nrf2, a basic leucine zipper transcription factor that regulates antioxidant protein expression, is recruited to the antioxidant responsive element (ARE) in the FTH promoter region, stimulating its transcription (41). IL-1β has also been shown to have a direct effect on a 5′ Fig.…”

Section: Heavy Chain Ferritin During Inflammationmentioning

confidence: 56%

Hyperferritinemia and inflammation

Kernan

Carcillo

2017

International Immunology

476

407

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Understanding of ferritin biology has traditionally centered on its role in iron storage and homeostasis, with low ferritin levels indicative of deficiency and high levels indicative of primary or secondary hemochromatosis. However, further work has shown that iron, redox biology and inflammation are inexorably linked. During infection, increased ferritin levels represent an important host defense mechanism that deprives bacterial growth of iron and protects immune cell function. It may also be protective, limiting the production of free radicals and mediating immunomodulation. Additionally, hyperferritinemia is a key acute-phase reactants, used by clinicians as an indication for therapeutic intervention, aimed at controlling inflammation in high-risk patients. One school of thought maintains that hyperferritinemia is an 'innocent bystander' biomarker of uncontrolled inflammation that can be used to gauge effectiveness of intervention. Other schools of thought maintain that ferritin induction could be a protective negative regulatory loop. Others maintain that ferritin is a key mediator of immune dysregulation, especially in extreme hyperferritinemia, via direct immune-suppressive and pro-inflammatory effects. There is a clear need for further investigation of the role of ferritin in uncontrolled inflammatory conditions both as a biomarker and mediator of disease because its occurrence identifies patients with high mortality risk and its resolution predicts their improved survival.

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“…CoCl 2 -treated cells were used as a model of chemical hypoxia-induced injury; however, there are several other effects of hypoxia that are not achieved by treatment with CoCl 2 . For example, CoCl 2 may stabilize the expression of hypoxia-inducible factor 1α (HIF-1α) (46,47). Second, the mechanisms underlying the antioxidant and anti-apoptotic properties of α-MG are not fully elucidated, and continued research is required in the future.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of α-mangostin against CoCl2-induced apoptosis by suppressing oxidative stress in H9C2 rat cardiomyoblasts

Zhao

Luo

2018

Mol Med Report

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Garcinia mangostana (a fruit) has been commonly used as a traditional drug in the treatment of various types of diseases. The aim of the present study was to evaluate the potential protective effect of α‑mangostin (α‑MG), a primary constituent extracted from the hull of the G. mangostana fruit (mangosteen), against CoCl2‑induced apoptotic damage in H9C2 rat cardiomyoblasts. α‑MG was demonstrated to significantly improve the viability of the CoCl2‑treated cells by up to 79.6%, attenuating CoCl2‑induced damage. Further studies revealed that α‑MG exerted a positive effect in terms of decreased reactive oxygen species generation, malondialdehyde concentration, cellular apoptosis, and increased superoxide dismutase activity. Furthermore, treatment with CoCl2 increased the cleavage of caspase‑9, caspase‑3 and apoptosis regulator BAX, and reduced apoptosis regulator Bcl‑2 in H9C2 cells, as measured by reverse transcription‑quantitative polymerase chain reaction and western blotting, which were significantly reversed by co‑treatment with α‑MG (0.06 and 0.3 mM). In conclusion, these results demonstrated that α‑MG protects H9C2 cells against CoCl2‑induced hypoxic injury, indicating that α‑MG is a potential therapeutic agent for cardiac hypoxic injury.

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Distinct regulatory mechanisms of the human ferritin gene by hypoxia and hypoxia mimetic cobalt chloride at the transcriptional and post-transcriptional levels

Cited by 40 publications

References 51 publications

A HIF-Independent Mediator of Transcriptional Responses to Oxygen Deprivation in Caenorhabditis elegans

A HIF-Independent Mediator of Transcriptional Responses to Oxygen Deprivation in Caenorhabditis elegans

Hyperferritinemia and inflammation

Protective effect of α-mangostin against CoCl2-induced apoptosis by suppressing oxidative stress in H9C2 rat cardiomyoblasts

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