Hypoxia decreases the expression of the two enzymes responsible for producing linear and cyclic tetrapyrroles in the heme biosynthetic pathway

Vargas, Patrick D.; Furuyama, Kazumichi; Sassa, Shigeru; Shibahara, Shigeki

doi:10.1111/j.1742-4658.2008.06723.x

Cited by 17 publications

(17 citation statements)

References 52 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Despite the absence of a canonical CCAAT consensus in its promoter, an approximate 3.5-fold Php4-dependent de-repression was observed (Mercier et al 2008). Recently, it was also demonstrated in hepatic cells that PBGD transcripts are reduced under hypoxia (Vargas et al 2008). …”

Section: Porphobilinogen Deaminase (Ec 4318)mentioning

confidence: 98%

“…pombe (Mercier et al 2008) and hypoxia-dependent repression in human hepatic UROS (Vargas et al 2008), no data is available upon regulation of UROS. On the other hand, UROS is not expected to become rate limiting as its substrate is unstable and its product is required for both heme synthesis as well as siroheme synthesis, which forms a branch point in the pathway.…”

Section: Uroporphyrinogen III Synthase (Ec 42175)mentioning

confidence: 99%

See 1 more Smart Citation

Heme biosynthesis and its regulation: towards understanding and improvement of heme biosynthesis in filamentous fungi

Franken

Lokman²,

Ram

et al. 2011

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

Heme biosynthesis in fungal host strains has acquired considerable interest in relation to the production of secreted heme-containing peroxidases. Class II peroxidase enzymes have been suggested as eco-friendly replacements of polluting chemical processes in industry. These peroxidases are naturally produced in small amounts by basidiomycetes. Filamentous fungi like Aspergillus sp. are considered as suitable hosts for protein production due to their high capacity of protein secretion. For the purpose of peroxidase production, heme is considered a putative limiting factor. However, heme addition is not appropriate in large-scale production processes due to its high hydrophobicity and cost price. The preferred situation in order to overcome the limiting effect of heme would be to increase intracellular heme levels. This requires a thorough insight into the biosynthetic pathway and its regulation. In this review, the heme biosynthetic pathway is discussed with regards to synthesis, regulation, and transport. Although the heme biosynthetic pathway is a highly conserved and tightly regulated pathway, the mode of regulation does not appear to be conserved among eukaryotes. However, common factors like feedback inhibition and regulation by heme, iron, and oxygen appear to be involved in regulation of the heme biosynthesis pathway in most organisms. Therefore, they are the initial targets to be investigated in Aspergillus niger.Electronic supplementary materialThe online version of this article (doi:10.1007/s00253-011-3391-3) contains supplementary material, which is available to authorized users.

show abstract

Section: Porphobilinogen Deaminase (Ec 4318)mentioning

confidence: 98%

Section: Uroporphyrinogen III Synthase (Ec 42175)mentioning

confidence: 99%

Heme biosynthesis and its regulation: towards understanding and improvement of heme biosynthesis in filamentous fungi

Franken

Lokman²,

Ram

et al. 2011

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…The lentiviruses pCCL.ET.GFP.sin, pCCL.ET.Flvcr1a-myc, pCCL.ET.Flvcr1b-myc, which express GFP, murine Flvcr1a-myc, or murine Flvcr1b-myc under the control of the enhanced transthyretin promoter, were produced in HEK293FT cells as previously described (37)(38)(39). HeLa and K562 cells were infected with the lentiviruses in the presence of Sequa-brene.…”

Section: Discussionmentioning

confidence: 99%

The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation

Chiabrando

Marro²,

Mercurio³

et al. 2012

J. Clin. Invest.

165

235

View full text Add to dashboard Cite

Feline leukemia virus subgroup C receptor 1 (FLVCR1) is a cell membrane heme exporter that maintains the balance between heme levels and globin synthesis in erythroid precursors. It was previously shown that Flvcr1-null mice died in utero due to a failure of erythropoiesis. Here, we identify Flvcr1b, a mitochondrial Flvcr1 isoform that promotes heme efflux into the cytoplasm. Flvcr1b overexpression promoted heme synthesis and in vitro erythroid differentiation, whereas silencing of Flvcr1b caused mitochondrial heme accumulation and termination of erythroid differentiation. Furthermore, mice lacking the plasma membrane isoform (Flvcr1a) but expressing Flvcr1b had normal erythropoiesis, but exhibited hemorrhages, edema, and skeletal abnormalities. Thus, FLVCR1b regulates erythropoiesis by controlling mitochondrial heme efflux, whereas FLVCR1a expression is required to prevent hemorrhages and edema. The aberrant expression of Flvcr1 isoforms may play a role in the pathogenesis of disorders characterized by an imbalance between heme and globin synthesis.

show abstract

“…Sequences of oligonucleotides for probes are indicated by the horizontal bar in the relevant figures. Nuclear extracts were prepared, as described previously, 23 from K562 cells or HEK293 human embryonic kidney cells that were transfected with a GATA1-FLAG fusion protein expression vector or its backbone vector.…”

Section: Electrophoretic Mobility Shift Assaymentioning

confidence: 99%

Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia

et al. 2013

View full text Add to dashboard Cite

© F e r r a t a S t o r t i F o u n d a t i o nsequence of primers and probes used in this study are listed in the Online Supplementary Tables. Polymerase chain reaction-based quantitative chromatin immunoprecipitationReal-time PCR-based quantitative chromatin immunoprecipitation (ChIP-qPCR) analysis was conducted essentially as previously described. 22 Electrophoretic mobility shift assayElectrophoretic mobility shift assay (EMSA) was performed using "DIG Gel Shift Kit, 2 nd Generation" (Roche Diagnostics GmbH, Mannheim, Germany), according to the manufacturer's protocol. Sequences of oligonucleotides for probes are indicated by the horizontal bar in the relevant figures. Nuclear extracts were prepared, as described previously, 23 from K562 cells or HEK293 human embryonic kidney cells that were transfected with a GATA1-FLAG fusion protein expression vector or its backbone vector. Promoter/enhancer activity assaysEach target DNA fragment was prepared from genomic DNA from normal volunteers (WT) or patients with CSA (referred to as "GGTA" or "delGATA" in each reporter construct) and was cloned into pGL3basic plasmid (Promega Corporation, Madison, WI, USA). The human ALAS2 proximal promoter region (g.4820_5115, between -267 and +29 from the transcription start site) 16,24 was cloned into the multiple-cloning site of pGL3basic [referred to as pGL3-AEpro (-267)]. A single DNA fragment (5.2 kbp), carrying the ALAS2 proximal promoter, first exon, first intron and the untranslated region of the second exon, was subcloned into the multiple cloning site of pGL3basic [referred to as pGL3-AEpro(-267)+intron1]. A DNA fragment containing the GATA1-binding region in the first intron of the ALAS2 gene (corresponding to g.7488_7960), which was defined by ChIP-seq analysis, 22 is referred to as the ChIP-peak. The length of the WT ChIP-peak is 473 bp. In addition, a 130-bp fragment containing ALAS2int1GATA, the consensus sequence for the GATA1-binding site in the ChIP-peak, is referred to as ChIPmini. Several deletion mutants of ChIPmini were prepared using pGL3-AEpro(-267)+ChIPmini(WT) as a template. The pGL3-TKpro plasmid was constructed by cloning herpes simplex virus thymidine kinase promoter into the multiple cloning site of pGL3basic plasmid. Each reporter vector and pEF-RL25 were introduced into K562 cells or HEK293 cells. Luciferase activity was determined using a dualluciferase reporter system (Promega).Disruption of a GATA binding element causes CSA haematologica | 2014; 99 (2) 253 Figure 1. Identification of a functional GATA1 element in the first intron of the ALAS2 gene. (A) Chromatin immunoprecipitation assay. Fragmented genomic DNA segments were immunoprecipitated with anti-GATA1 antibody or control IgG, and then precipitated fragments were quantified using real-time PCR as described in the Online Supplementary Methods. PC or NC indicates positive control or negative control, respectively, for the ChIP assay using anti-GATA1 in K562 cells. 22 One GATA element is present in the proximal promoter region and ...

show abstract

Hypoxia decreases the expression of the two enzymes responsible for producing linear and cyclic tetrapyrroles in the heme biosynthetic pathway

Cited by 17 publications

References 52 publications

Heme biosynthesis and its regulation: towards understanding and improvement of heme biosynthesis in filamentous fungi

Heme biosynthesis and its regulation: towards understanding and improvement of heme biosynthesis in filamentous fungi

The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation

Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia

Contact Info

Product

Resources

About