Erythrocyte Organic Phosphates and Hemoglobin Function in Birds, Reptiles, and Fishes

Isaacks, R. E.; Harkness, Donald R.

doi:10.1093/icb/20.1.115

Cited by 87 publications

(26 citation statements)

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“…They have been reported to have extracellular actions in the central nervous system (Vallejo et al, 1987), but their only known intracellular function is the modulation of oxygen-binding affinity of haemoglobin in avian erythrocytes (Isaacks and Harkness, 1980). The present results support the previous proposal (Balla et al, 1989a) that their function(s) might be related to long-term cellular responses.…”

Section: Discussionsupporting

confidence: 90%

Inositol polyphosphates are not increased by overexpression of Ins(1,4,5)P3 3-kinase but show cell-cycle dependent changes in growth factor-stimulated fibroblasts.

Balla

Sim

Báukal

et al. 1994

MBoC

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NIH 3T3 fibroblasts were stably transfected with rat brain inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) 3-kinase to explore the relationship between increased production of Ins(1,3,4,5)P4 and the formation of InsP5 and InsP6. Mass measurements of InsP5 and InsP6 revealed no significant difference between kinase- and vector-transfected fibroblasts. However, such 3-kinase-transfected cells, when labeled with [3H]inositol for 48-72 h, showed lower levels of [3H]InsP5 and [3H]InsP6, as well as [3H]Ins(1,3,4,6)P4 and D/L[3H]Ins(1,4,5,6)P4, than their vector-transfected counterparts. Because Ins(1,4,5)P3 3-kinase-transfected cells grew less rapidly than vector-transfected controls, we determined whether the synthesis of InsP5 and InsP6 was related to a specific phase of the cell cycle. When NIH 3T3 cells prelabeled with [3H]inositol were synchronized by serum deprivation followed by stimulation with platelet-derived growth factor (PDGF), the amounts of labeled InsP5 and InsP6 began to increase only after 12 h of stimulation, when cells entered the S-phase as indicated by increased [3H]thymidine incorporation. The enhanced synthesis of these inositol polyphosphates was preceded by an early increase in Ins(1,4,5)P3 and its metabolites that was no longer evident by the fifth hour of PDGF action. There was also a prominent and biphasic increase in the level of D/L-Ins(1,4,5,6)P4 with an early peak at approximately 3 h and a second rise that paralleled the increases in InsP5 and InsP6. These results indicate that the formation of highly phosphorylated inositols is not tightly coupled to the receptor-mediated formation of Ins(1,4,5)P3 and its metabolites but is mainly determined by other factors that operate at specific points of the cell cycle.

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Section: Discussionsupporting

confidence: 90%

Inositol polyphosphates are not increased by overexpression of Ins(1,4,5)P3 3-kinase but show cell-cycle dependent changes in growth factor-stimulated fibroblasts.

Balla

Sim

Báukal

et al. 1994

MBoC

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“…The major organic phosphate in human red blood cells is bisphosphoglycerate, whereas that in chicken erythrocytes is inositol pentaphosphate (60). Most in vitro studies utilize the more readily available IHP.…”

Section: Discussionmentioning

confidence: 99%

The Structural and Functional Analysis of the Hemoglobin D Component from Chicken

Knapp

Oliveira

Xie

et al. 1999

Journal of Biological Chemistry

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Oxygen binding by chicken blood shows enhanced cooperativity at high levels of oxygen saturation. This implies that deoxy hemoglobin tetramers self-associate. The crystal structure of an R-state form of chicken hemoglobin D has been solved to 2.3-Å resolution using molecular replacement phases derived from human oxyhemoglobin. The model consists of an ␣ 2 ␤ 2 tetramer in the asymmetric unit and has been refined to a R-factor of 0.222 (R-free ‫؍‬ 0.257) for 29,702 reflections between 10.0-and 2.3-Å resolution. Chicken Hb D differs most from human oxyhemoglobin in the AB and GH corners of the ␣ subunits and the EF corner of the ␤ subunits. Reanalysis of published oxygen binding data for chicken Hbs shows that both chicken Hb A and Hb D possess enhanced cooperativity in vitro when inositol hexaphosphate is present. The electrostatic surface potential for a calculated model of chicken deoxy-Hb D tetramers shows a pronounced hydrophobic patch that involves parts of the D and E helices of the ␤ subunits. This hydrophobic patch is a promising candidate for a tetramer-tetramer interface that could regulate oxygen binding via the distal histidine.The oxygen binding curves of chicken blood samples taken at different stages of development exhibit Hill coefficients which exceed 4.0 (super-cooperativity) at oxygen saturation levels between 70 and 90% oxygenation (1-5). Elevated levels of oxygen-binding cooperativity should be advantageous because such hemoglobins (Hbs) 1 would deliver a greater quantity of oxygen to the tissues under normal physiological conditions. Super-cooperativity has also been observed in the blood and Hbs of several species of amphibians (6 -8), reptiles (9 -10), other birds (1, 11), and embryonic mammals (12-14). Although incomplete oxygen saturation resulted in spuriously high Hill coefficients in much of the early data (see , the data of Lapennas and Reeves (5) on chicken blood and Holland et al.(12-14) on embryonic marsupial blood were obtained at saturating pressures of O 2 .The blood of adult chickens, as in most other birds, is composed of two Hb components that have identical ␤ chains but differ in the sequences of the ␣ subunits. Hb A (␣ The cooperative binding of oxygen by tetrameric Hbs arises from the transition of the Hb from a conformation with a low oxygen affinity (T-state) to a conformation with a high oxygen affinity (R-state) (21,22). Much of our understanding of this process has come from the crystallographic analysis of the unligated (T-state) and ligated (R-state) structures of both human Hb A (23-26) and horse . Although a structural explanation of super-cooperativity requires the crystallographic analysis of both the R-and T-state forms of chicken Hb D, the analysis of intermediate structures are likely to be necessary for understanding the mechanism of cooperativity because knowledge of two thermodynamic states does not itself determine the pathway between them. We report here the structure of an R-state form of chicken Hb D solved with diffraction data to 2.3-Å resolution. Th...

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“…Higher-order inositol phosphates have been described in several systems. InsP5 has been described in avian erythrocytes (27), where it serves to alter the oxygen-hemoglobin dissociation curve in much the same way that 2,3-diphosphoglycerate does in mammalian erythrocytes (28). InsP6 or phytic acid is a prominent component of plant seeds (29).…”

Section: Discussionmentioning

confidence: 99%

Perturbation of the human T-cell antigen receptor-T3 complex leads to the production of inositol tetrakisphosphate: evidence for conversion from inositol trisphosphate.

Stewart¹,

Prpić²,

Powers³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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Antibodies directed against the T-cell antigen receptor-T3 complex mimic antigen and lead to cellular changes consistent with activation. When cells of the human T-cell line Jurkat were stimulated with a monoclonal antibody directed against T3, inositol phosphates were produced. In addition to inositol trisphosphate, which is the product of phosphatidylinositol bisphosphate cleavage, a second inositol polyphosphate was formed. This compound was more polar than inositol trisphosphate but less polar than inositol pentakisphosphate. It cochromatographed with inositol tetrakisphosphate from ostrich erythrocytes. In permeabilized Jurkat cells, this compound was shown to be formed from inositol 1,4,5-trisphosphate, but only in the presence of ATP, and 32p was incorporated into it from [y-32P]ATP. There also was coincident formation of inositol 1,3,4-trisphosphate. We conclude that the more polar compound is inositol tetrakisphosphate, which is formed by phosphorylation of inositol 1,4,5-trisphosphate and may be the precursor of inositol 1,3,4-trisphosphate.Activation of several receptor-mediated cellular systems has been shown to be calcium dependent and mediated by breakdown products of polyphosphate derivatives of phosphatidylinositol (1-6). In these systems, stimulation of the relevant receptor leads to phosphodiesterase (phospholipase C)-catalyzed cleavage of phosphatidylinositol bisphosphate to inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and 1,2-diacylglycerol (4, 5). In turn, Ins(1,4,5)P3 and diacylglycerol act as second messengers to release intracellular stores of calcium and activate protein kinase C (6), respectively. Antibodies directed against the T-lymphocyte receptor for nominal antigen or its closely associated structure, T3 (Leu-4) have been shown to mimic antigen (7) and lead to changes characteristic of activation. These changes include production of lymphokines (8) and interleukin-2 receptors (9) and proliferation (10, 11). In a series of papers (12-14), Stobo and colleagues have shown that perturbation of the T-cell receptor-T3 complex on cells of the human T-cell leukemia line Jurkat leads to production of inositol phosphates (14) and rapid increases in intracellular calcium concentration (12,13). Furthermore, in studies using permeabilized Jurkat cells, they have demonstrated that addition of inositol trisphosphate causes release of calcium from iniracellular stores (14).We report here that perturbation of the T-cell antigen receptor-T3 complex with a monoclonal antibody leads to the production of not only Ins(1,4,5)P3, but also a second inositol polyphosphate. We present evidence that this compound isThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. inositol tetrakisphosphate (InsP4). Furthermore, we present evidence that it is generated by the ATP-dependent phosphorylation of Ins(1,4,5)P3. MATERIALS AND METHODSCells and Antibo...

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Erythrocyte Organic Phosphates and Hemoglobin Function in Birds, Reptiles, and Fishes

Cited by 87 publications

References 0 publications

Inositol polyphosphates are not increased by overexpression of Ins(1,4,5)P3 3-kinase but show cell-cycle dependent changes in growth factor-stimulated fibroblasts.

Inositol polyphosphates are not increased by overexpression of Ins(1,4,5)P3 3-kinase but show cell-cycle dependent changes in growth factor-stimulated fibroblasts.

The Structural and Functional Analysis of the Hemoglobin D Component from Chicken

Perturbation of the human T-cell antigen receptor-T3 complex leads to the production of inositol tetrakisphosphate: evidence for conversion from inositol trisphosphate.

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