Ferritins (FTs) are iron storage proteins that are involved in managing iron‐oxygen balance. In our work, we present a hypothesis on the putative effect of geological changes that have affected the evolution and radiation of ferritin proteins. Based on sequence analysis and phylogeny reconstruction, we hypothesize that two significant factors have been involved in the evolution of ferritin proteins: fluctuations of atmospheric oxygen concentrations, altering redox potential, and changing availability of water rich in bioavailable ferric ions.Fish, ancient amphibians, reptiles, (...) and placental mammals developed the broadest repertoire of singular FTs, attributable to embryonic growth in aquatic environments containing low oxygen levels and abundant forms of soluble iron. In contrast, oviparous land vertebrates, like reptiles and birds, that have developed in high oxygen levels and limited levels of environmental Fe2+ exhibit a lower diversity of singular FTs, but display a broad repertoire of subfamilies, particularly notable in early reptiles. (shrink)

Iron delivered by transferrin to the interior of the cell is in part utilized in biosynthetic processes and in part incorporated into ferritin, the major iron storage protein. The intracellular ferritin concentration is directly correlated to and determined by the extent of iron supply to the cell. Intracellular partitioning of iron to ferritin is suggested as forming the basis of cellular iron homeostasis.

The expression of certain eukaryotic genes is – at least in part – controlled at the level of mRNA translation. The step of translational initiation represents the primary target for regulation. The regulation of the intracellular iron storage protein ferritin in response to iron levels provides a good example of translational control by a reversible RNA/protein interaction in the 5' untranslated region of an mRNA. We consider mechanisms by which mRNA/protein interactions may impede translation initiation and discuss recent data suggesting (...) that the ferritin example may represent the ‘tip of the iceberg’ of a more general theme for translational control. (shrink)

De Marco and colleagues claim that the standard account of invasiveness as commonly encountered ‘…does not capture all uses of the term in relation to medical interventions1 ’. This is open to challenge. Their first example is ‘non-invasive prenatal testing’. Because it involves puncturing the skin to obtain blood, De Marco et al take this as an example of how an incision or insertion is not sufficient to make an intervention invasive; here is a procedure that involves an incision, but (...) it is regarded as non-invasive. However, this ignores the context, and the term should really be understood in reference to the fetus. It is hard to believe healthcare professionals regard taking blood to measure, for example, ferritin levels as invasive but taking blood to look for fragments of fetal DNA as not. If anyone uses the term thinking it is not invasive to the mother, the solution would be to call it invasive, not redefine what is invasive. De Marco and colleagues’ second example is describing electroconvulsive therapy (ECT) as invasive. However, this is not borne out by their referenced papers. The first cited source is about non-invasive brain stimulation2 and only contains a single sentence about ECT. This sentence may suggest that their view is that ECT …. (shrink)

It is hypothesized that iron from biological tissues, liberated during decay, may have played a role in inhibiting loss of anatomical information during fossilization of extinct organisms. Most tissues in the animal kingdom contain iron in different forms. A widely distributed iron‐bearing molecule is ferritin, a globular protein that contains iron crystallites in the form of ferrihydrite minerals. Iron concentrations in ferritin are high and ferrihydrites are extremely reactive. When ancient animals are decaying on the sea floor under anoxic environmental (...) conditions, ferrihydrites may initialize the selective replication of some tissues in pyrite FeS2. This model explains why some labile tissues are preserved, while other more resistant structures decay and are absent in many fossils. A major implication of this hypothesis is that structures described as brains in Cambrian arthropods are not fossilization artifacts, but are instead a source of information on anatomical evolution at the dawn of complex animal life. (shrink)

Carbon monoxide (CO), a product of organic oxidation processes, arises in vivo during cellular metabolism, most notably heme degradation. CO binds to the heme iron of most hemoproteins. Tissue hypoxia following hemoglobin saturation represents a principle cause of CO‐induced mortality in higher organisms, though cellular targets cannot be excluded. Despite extreme toxicity at high concentrations, low concentrations of CO can confer cytoprotection during ischemia/reperfusion or inflammation‐induced tissue injury. Likewise, heme oxygenase, an enzyme that produces CO, biliverdin and iron, as well (...) as a secondary increase in ferritin synthesis, from the oxidation of heme, can confer protection in vivo and in vitro. CO has been shown to affect several intracellular signaling pathways, including guanylate cyclase, which generates guanosine 3′:5′ cyclic monophosphate and the mitogen‐activated protein kinases (MAPK). Such pathways mediate, in part, the known vasoregulatory, anti‐inflammatory, anti‐apoptotic and anti‐proliferative effects of this gas. Exogenous CO delivered at low concentrations is showing therapeutic potential as an anti‐inflammatory agent and as such can modulate numerous pathophysiological states. This review will delve into the biological significance and medical applications of this gas molecule. BioEssays 26:270–280, 2004. © 2004 Wiley Periodicals, Inc. (shrink)