Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vibrio vulnificus can use the standard iron chelator deferoxamine (Desferal) for efficient iron-uptake via the specific receptor DesA, which is encoded by desA. We investigated the ubiquity of the deferoxamine-mediated iron-uptake system in V. vulnificus strains and the potential risk of the system. By polymerase chain reaction (PCR), desA was found in 10 of 10 clinical strains and in 9 of 10 environmental strains, and their growth was stimulated by deferoxamine. By reverse-transcriptase PCR, desA was expressed only under iron-limited conditions containing deferoxamine. V. vulnificus growth in the presence of deferoxamine was suppressed by desA mutation, and the suppressed growth was recovered by desA complementation. Deferoxamine stimulated V. vulnificus growth in iron-limited in vitro and ex vivo backgrounds containing transferrin-bound iron. Overall, V. vulnificus can use transferrin-bound iron via the widespread deferoxamine-mediated iron-uptake system; this cautions that deferoxamine therapy in patients with iron overload may increase the risk of fatal infections caused by V. vulnificus.
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PMID:A widespread deferoxamine-mediated iron-uptake system in Vibrio vulnificus. 1800 34

Perturbation in iron homeostasis is a hallmark of some hematologic diseases. Abnormal sideroblasts with accumulation of iron in the mitochondria are named ring sideroblasts (RS). RS is a cardinal feature of refractory anemia with RS (RARS) and RARS with marked thrombocytosis (RARS/-T). Mutations in SF3B1, a member of the RNA splicing machinery are frequent in RARS/-T and defects of this gene were linked to RS formation. Here we showcase the differences in iron architecture of SF3B1-mutant and wild-type (WT) RARS/-T and provide new mechanistic insights by which SF3B1 mutations lead to differences in iron. We found higher iron levels in SF3B1 mutant vs WT RARS/-T by transmission electron microscopy/spectroscopy/flow cytometry. SF3B1 mutations led to increased iron without changing the valence as shown by the presence of Fe(2+) in mutant and WT. Reactive oxygen species and DNA damage were not increased in SF3B1-mutant patients. RNA-sequencing and Reverse transcriptase PCR showed higher expression of a specific isoform of SLC25A37 in SF3B1-mutant patients, a crucial importer of Fe(2+) into the mitochondria. Our studies suggest that SF3B1 mutations contribute to cellular iron overload in RARS/-T by deregulating SLC25A37.
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PMID:Distinct iron architecture in SF3B1-mutant myelodysplastic syndrome patients is linked to an SLC25A37 splice variant with a retained intron. 2485 90