Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sickle cell anaemia (SCA) patients have a high risk of infection. We retrospectively investigated the prevalence of infection among SCA patients from Bahia, Brazil. A total of 1415 SCA patients were studied between 1995 and 2009: 190 (13.4%) had hepatitis C virus (HCV), 67 (4.7%) had human T-lymphotropic virus type I (HTLV-I), 44 (3.1%) had hepatitis B virus (HBV), 40 (2.8%) had Chagas' disease, 11 (0.8%) had human immunodeficiency virus (HIV), and 5 (0.4%) had syphilis. Patients with HCV infection had a higher risk of hospitalisation (OR=1.52, 95% Cl: 1.07-2.17, P=0.020), bone disorders (OR=1.94, 95% Cl: 1.15-3.27, P=0.011), stroke (OR=2.17, 95% Cl: 1.12-4.14, P=0.017), painful crisis (OR=1.61, 95% Cl: 1.17-2.22, P=0.004) and leg ulcers (OR=1.61, 95% Cl: 1.04-3.03, P=0.031). Patients with HBV infection had a higher risk for bone disorders (OR=4.90, 95% Cl: 2.08-11.54, P<.010), stroke (OR=3.01, 95% Cl: 1.29-6.04, P=0.007), painful crisis (OR=3.51, 95% Cl: 1.62-7.63, P<0.001), acute chest syndrome (ACS) (OR=2.66, 95% Cl: 1.34-5.28, P=0.004), leg ulcers (OR=6.60, 95% Cl: 3.37-12.91, P<.001) and vaso-occlusive crisis (OR=6.34, 95% Cl: 1.96-20.66, P<0.001). Patients with HTLV-I infection had a high risk for bone disorders (OR=2.94, 95% Cl: 1.28-6.74, P=0.011), respiratory failure (OR=2.66, 95% Cl: 1.26-5.51, P=0.012), leg ulcers (OR=3.27, 95% Cl: 1.69-6.11, P<.001), painful crisis (OR=1.82, 95% Cl: 1.07-3.13, P=0.025) and ACS (OR=1.85, 95% Cl: 1.10-3.41, P<.047). SCA patients with HCV infection had increased triglycerides and low-density lipoprotein cholesterol (P=0.036; P=0.027), iron serum (P=0.016) and ferritin (P=0.007). These results reveal important roles for these infections in SCA patients' clinical outcomes, and studies are warranted to determine the mechanisms utilised by these agents and their involvement in disease severity.
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PMID:The association of infection and clinical severity in sickle cell anaemia patients. 2121 18

Oxidative damage contributes to microbe elimination during macrophage respiratory burst. Nuclear factor, erythroid-derived 2, like 2 (NRF2) orchestrates antioxidant defenses, including the expression of heme-oxygenase-1 (HO-1). Unexpectedly, the activation of NRF2 and HO-1 reduces infection by a number of pathogens, although the mechanism responsible for this effect is largely unknown. We studied Trypanosoma cruzi infection in mice in which NRF2/HO-1 was induced with cobalt protoporphyrin (CoPP). CoPP reduced parasitemia and tissue parasitism, while an inhibitor of HO-1 activity increased T. cruzi parasitemia in blood. CoPP-induced effects did not depend on the adaptive immunity, nor were parasites directly targeted. We also found that CoPP reduced macrophage parasitism, which depended on NRF2 expression but not on classical mechanisms such as apoptosis of infected cells, induction of type I IFN, or NO. We found that exogenous expression of NRF2 or HO-1 also reduced macrophage parasitism. Several antioxidants, including NRF2 activators, reduced macrophage parasite burden, while pro-oxidants promoted it. Reducing the intracellular labile iron pool decreased parasitism, and antioxidants increased the expression of ferritin and ferroportin in infected macrophages. Ferrous sulfate reversed the CoPP-induced decrease in macrophage parasite burden and, given in vivo, reversed their protective effects. Our results indicate that oxidative stress contributes to parasite persistence in host tissues and open a new avenue for the development of anti-T. cruzi drugs.
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PMID:Oxidative stress fuels Trypanosoma cruzi infection in mice. 2272 29

Iron is an essential element for most organisms However, free iron and heme, its complex with protoporphyrin IX, can be extremely cytotoxic, due to the production of reactive oxygen species, eventually leading to oxidative stress. Thus, eukaryotic cells control iron availability by regulating its transport, storage and excretion as well as the biosynthesis and degradation of heme. In the genome of Rhodnius prolixus, the vector of Chagas disease, we identified 36 genes related to iron and heme metabolism We performed a comprehensive analysis of these genes, including identification of homologous genes described in other insect genomes. We observed that blood-meal modulates the expression of ferritin, Iron Responsive protein (IRP), Heme Oxygenase (HO) and the heme exporter Feline Leukemia Virus C Receptor (FLVCR), components of major pathways involved in the regulation of iron and heme metabolism, particularly in the posterior midgut (PM), where an intense release of free heme occurs during the course of digestion. Knockdown of these genes impacted the survival of nymphs and adults, as well as molting, oogenesis and embryogenesis at different rates and time-courses. The silencing of FLVCR caused the highest levels of mortality in nymphs and adults and reduced nymph molting. The oogenesis was mildly affected by the diminished expression of all of the genes whereas embryogenesis was dramatically impaired by the knockdown of ferritin expression. Furthermore, an intense production of ROS in the midgut of blood-fed insects occurs when the expression of ferritin, but not HO, was inhibited. In this manner, the degradation of dietary heme inside the enterocytes may represent an oxidative challenge that is counteracted by ferritins, conferring to this protein a major antioxidant role. Taken together these results demonstrate that the regulation of iron and heme metabolism is of paramount importance for R. prolixus physiology and imbalances in the levels of these key proteins after a blood- meal can be extremely deleterious to the insects in their various stages of development.
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PMID:Silencing of Iron and Heme-Related Genes Revealed a Paramount Role of Iron in the Physiology of the Hematophagous Vector Rhodnius prolixus. 2945 53