Neocytolysis is the hypothesis formulated to explain experimental evidence of selective lysis of young red blood cells (RBCs) (neocytes) associated with decreased plasma levels of erythropoietin (EPO). In humans, it appears to take place whenever a fast RBC mass reduction is required, i.e., in astronauts during the first days of spaceflight under weightlessness, where a fast reduction in plasma volume and increase in haematocrit occur. EPO plasma levels then decline and a decrease in RBC mass takes place, apparently because of the selective lysis of the youngest, recently generated RBCs (neocytes). The same process seems to occur in people descending to sea level after acclimatization at high altitude. After descent, the polycythaemia developed at high altitude must be abrogated, and a rapid reduction in the number of circulating RBCs is obtained by a decrease in EPO synthesis and the lysis of what seem to be young RBCs. In vivo, neocytolysis seems to be abolished by EPO administration. More recent research has ascribed to neocytolysis the RBC destruction that occurs under such disparate pathophysiologic conditions as nephropathy, severe obstructive pulmonary disease, blood doping, and even malaria anaemia. According to the theory, EPO's central role would be not only to stimulate the production of new RBCs in conditions of anaemia, as maintained by the orthodox view, but also that of a cytoprotective factor for circulating young RBCs. Why neocytes are specifically destroyed and how is this related to decreased EPO levels has not yet been elucidated. Changes in membrane molecules of young RBCs isolated from astronauts or mountain climbers upon return to normal conditions seem to indicate a higher susceptibility of neocytes to ingestion by macrophages. By limiting the context to space missions and high altitude expeditions, this review will address unresolved and critical issues that in our opinion have not been sufficiently highlighted in previous works.
Red blood cell research is important for both, the clinical haematology, such as transfusion medicine or anaemia investigations, and the basic research fields like exploring general membrane physiology or rheology. Investigations of red blood cells include a wide spectrum of methodologies ranging from population measurements with a billion cells evaluated simultaneously to single-cell approaches. All methods have a potential for pitfalls, and the comparison of data achieved by different technical approaches requires a consistent set of standards. Here, we give an overview of common mistakes using the most popular methodologies in red blood cell research and how to avoid them. Additionally, we propose a number of standards that we believe will allow for data comparison between the different techniques and different labs. We consider biochemical analysis, flux measurements, flow cytometry, patch-clamp measurements and dynamic fluorescence imaging as well as emerging single-cell techniques, such as the use of optical tweezers and atomic force microscopy.
L-Methionine (L-Met) is the only sulphur-containing proteinogenic amino acid together with cysteine. Its importance is highlighted by it being the initiator amino acid for protein synthesis in all known living organisms. L-Met, free or inserted into proteins, is sensitive to oxidation of its sulfide moiety, with formation of L-Met sulfoxide. The sulfoxide could not be inserted into proteins, and the oxidation of L-Met in proteins often leads to the loss of biological activity of the affected molecule. Key discoveries revealed the existence, in rats, of a metabolic pathway for the reduction of free L-Met sulfoxide and, later, in Escherichia coli, of the enzymatic reduction of L-Met sulfoxide inserted in proteins. Upon oxidation, the sulphur atom becomes a new stereogenic center, and two stable diastereoisomers of L-Met sulfoxide exist. A fundamental discovery revealed the existence of two unrelated families of enzymes, MsrA and MsrB, whose members display opposite stereospecificity of reduction for the two sulfoxides. The importance of Msrs is additionally emphasized by the discovery that one of the only 25 selenoproteins expressed in humans is a Msr. The milestones on the road that led to the discovery and characterization of this group of antioxidant enzymes are recounted in this review.
Human erythrocyte band 3 becomes rapidly phosphorylated on tyrosine residues after exposure of erythrocytes to hypertonic conditions. The driving force for this phosphorylation reaction seems to be a decrease in cell volume, because (1) changes in band 3 phosphotyrosine content accurately track repeated changes in erythrocyte volume through several cycles of swelling and shrinking; (2) the level of band 3 phosphorylation is independent of the osmolyte employed but strongly sensitive to the magnitude of cell shrinkage; and (3) exposure of erythrocytes to hypertonic buffers under conditions in which intracellular osmolarity increases but volume does not change (nystatin-treated cells) does not promote an increase in tyrosine phosphorylation. We hypothesize that shrinkage-induced tyrosine phosphorylation results either from an excluded-volume effect, stemming from an increase in intracellular crowding, or from changes in membrane curvature that accompany the decrease in cell volume. Although the net phosphorylation state of band 3 is shown to be due to a delicate balance between a constitutively active tyrosine phosphatase and constitutively active tyrosine kinase, the increase in phosphorylation during cell shrinkage was demonstrated to derive specifically from an activation of the latter. Further, a peculiar inhibition pattern of the volume-sensitive erythrocyte tyrosine kinase that matched that of p72syk, a tyrosine kinase already known to associate with band 3 in vivo, suggested the involvement of this kinase in the volume-dependent response.
The effect on the conformational-aggregational properties of pectate in aqueous solution brought by the addition of specific ions (H+, Ca 2 +, Cu 2 +) was studied by osmometric, microcalorimetric, dilatometric, and rheological methods. Evidence is provided for the intramolecular nature of the pH induced conformational transition. The addition of divalent ions brings about at the same time a conformational change of the chain of pectate and chain--chain association.The study of the interaction of pectate (and its partially esterified "derivatives", pectins) with specific ions in aqueous solutions is of fundamental importance to understand the properties of their solutions and gels at the molecular level. Indeed, pectate aqueous solutions in the presence of ions have been subjected to many investigations (1-5). However, only in a few cases has the "course" of the interaction been followed over a wide range of the ion to polymer molar ratio, R. The scrutiny of such a dependence for thermodynamic functions like ΔΗ has allowed us to disclose an intramolecular coopera tive conformational transition of pectate upon changing pH (5). Other properties investigated were consistent with the above interpretation. It was also suggested that the intramolecular conformational transition was a prerequisite for the further aggregation of chain mo lecules occurring in the gelling conditions at low pH. Direct evidence from molecular weight measurements will be provided here in favor of such a transition.Among the other parameters able to induce similar macroscopic effects, the addition of divalent cations is particularly effective. Literature data are in almost complete agreement with the view that an aggregation of chains induced by ions is responsible for the gel forma-
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