Disease relevance of alpha globin

• It is shown that neokyotorphin (the alpha-globin fragment 137-141) stimulates proliferation of normal cells (murine embryonic fibroblasts, red bone marrow and spleen cells) and tumor cells (murine melanoma and transformed fibroblasts L929) in the absence or in the presence of fetal bovine serum [1].

High impact information on alpha globin

• Using an in vitro-transcribed and polyadenylated alpha-globin 3'UTR, we have devised an in vitro mRNA decay assay which reproduces the alpha-complex-dependent mRNA stability observed in cells [2].
• Polarity of DNA replication through the avian alpha-globin locus [3].
• One of these regions is also found to be particularly conserved in the alpha-globin of birds and reptiles; birds and some turtles are known to modulate the oxygen affinity of their haemoglobin with inositol polyphosphate in the same way as with 2,3-bisphosphoglycerate in other species [4].
• The gene is located in the middle of the alpha-globin gene cluster of a marsupial, Sminthopsis macroura and of humans [5].
• The mammalian alphaD-globin gene lineage and a new model for the molecular evolution of alpha-globin gene clusters at the stem of the mammalian radiation [5].

Biological context of alpha globin

• The stable globin mRNAs provide an ideal system for studying the mechanism governing mammalian mRNA turnover. alpha-Globin mRNA stability is dictated by sequences in the 3' untranslated region (3'UTR) which form a specific ribonucleoprotein complex (alpha-complex) whose presence correlates with mRNA stability [2].
• However, a high concentration (up to 2.7 times over random sequences) of hexanucleotide factor sites is observed on small stretches of the alpha-globin gene MAR. (2) Some regulatory protein binding sites are underrepresented whereas others are overrepresented, giving to an MAR a particular transcription factor flavor [6].
• The B haplotype encodes two alpha-globin chains, Ialpha2 and IIalpha4, which differ at positions 10 and 11: Ialpha2 has 10 I1e, 11 Gln, 64 Asn; IIalpha4 has 10 Val, 11 Lys, 64 Asn [7].
• Apart from the Ala/Asn polymorphism at position 64, amino acid substitutions in allelic and nonallelic alpha-globin chains seem to have arisen by single point mutations [7].

Anatomical context of alpha globin

• IOVs from membranes incubated with alpha-globin chains or haemoglobin A were nearly normal (79 +/- 3% and 86 +/- 5% of controls, respectively) [8].
• These studies show that isolated beta-globin chains (but not alpha-globin chains) can produce a spectrin-binding defect in normal red cell membranes similar to that seen in alpha thalassaemia [8].

Associations of alpha globin with chemical compounds

• Blood was sampled every 14 d at 0 and 2 h after the morning feeding and analyzed for beta-hydroxybutyrate (beta HBA), glucose, nonesterified fatty acids, urea N, L(+) lactate, and VFA [9].

References