Role of hybrid tetramer formation in gelation of haemoglobin S

Bookchin, Robert M.; Nagel, Ronald L.; Balazs, Tania

doi:10.1038/256667a0

Cited by 73 publications

(15 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…7). The value for Hb F/Hb S mixtures was right shifted 0.5 unit from Hb S, indicating that the initiation of polymerization in these mixtures is controlled by Hb S, which represents about one-fourth of the total hemoglobin concentration (3,10). These results also suggest that Hb F, Hb A 2 , and FS hybrids are excluded from the initiation of polymerization with Hb S, while some A 2 S hybrids in the A 2 S mixture can participate in the formation of nuclei with Hb S.…”

Section: Resultsmentioning

confidence: 95%

“…Mixtures of Hb A 2 and Hb S, like mixtures of Hb F and Hb S, have a higher solubility than Hb S alone and result in inhibition of Hb S polymerization (1,2). The primary inhibitory effects of Hb A 2 and Hb F in these mixtures are to exclude the asymmetrical ␣ 2 ␤ S ␦ and ␣ 2 ␤ S ␥ hybrids, respectively, as well as Hb A 2 and Hb F from initiation of polymerization with Hb S (3)(4)(5)(6)(7)(8)(9)(10)(11). Studies comparing minimum gel concentrations for naturally occurring hemoglobin variants, including the Lepore (␦␤ hybrid) hemoglobins, suggested that Gln ␦87 and Ala ␦22 in Hb A 2 are important sites potentiating inhibition of polymerization of deoxy Hb S (5).…”

Section: From the Children's Hospital Of Philadelphia Division Of Hementioning

confidence: 99%

See 1 more Smart Citation

Polymerization of Three Hemoglobin A2 Variants Containing Valδ6 and Inhibition of Hemoglobin S Polymerization by Hemoglobin A2

Adachi

Pang

Reddy

et al. 1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

To understand determinants for hemoglobin (Hb) stability and Hb A 2 inhibition of Hb S polymerization, three Val ␦6 Hb A 2 variants (Hb A 2 ␦E6V, Hb A 2 ␦E6V,␦Q87T, and Hb A 2 ␦E6V,␦A22E,␦Q87T) were expressed in yeast, and stability to mechanical agitation and polymerization properties were assessed. Oxy forms of Hb A 2 ␦E6V and Hb A 2 ␦E6V,␦Q87T were 2-and 1.6-fold, respectively, less stable than oxy-Hb S, while the stability of Hb A 2 ␦E6V,␦A22E,␦Q87T was similar to that of Hb S, suggesting that Ala ␦22 and Gln ␦87 contribute to the surface hydrophobicity of Hb A 2 . Deoxy Hb A 2 ␦E6V polymerized without a delay time, like deoxy Hb F ␥E6V, while deoxy Hb A 2 ␦E6V,␦Q87T and deoxy Hb A 2 ␦E6V,␦A22E,␦Q87T polymerized after a delay time, like deoxy Hb S, suggesting that ␤87 Thr is required for the formation of nuclei. Deoxy Hb F ␥E6V,␥Q87T showed no delay time and required a 3.5-fold higher concentration than deoxy Hb S for polymerization, suggesting that Thr effects on Val

show abstract

Section: Resultsmentioning

confidence: 95%

Section: From the Children's Hospital Of Philadelphia Division Of Hementioning

confidence: 99%

Polymerization of Three Hemoglobin A2 Variants Containing Valδ6 and Inhibition of Hemoglobin S Polymerization by Hemoglobin A2

Adachi

Pang

Reddy

et al. 1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Por sua vez, a HbF constitui o maior inibidor da polimerização da desoxi-Hb S, em função da mesma se "misturar" melhor à HbS, formar "híbridos" e impedir a polimerização. 23,[56][57][58][59] Pacientes com baixa taxa de HbF podem apresentar, ainda, um quadro de esplenomegalia caracterizado pela congestão na polpa vermelha pelo seqüestro de eritrócitos falcizados nos cordões esplênicos e sinusóides, que evolui com a formação de trombose e infartos, culminando com a atrofia e fibrose do órgão. Esse fenômeno ocorre geralmente até os cinco anos de idade.…”

Section: A Importância Da Hemoglobina Fetal Na Clínica Da Anemia Falcunclassified

Importância da avaliação da hemoglobina fetal na clínica da anemia falciforme

Mousinho-Ribeiro¹,

Cardoso²,

Sousa³

et al. 2008

Rev. Bras. Hematol. Hemoter.

View full text Add to dashboard Cite

De todos esses quadros, o mais importante é a homozigose para o gene HbS ou anemia falciforme (AF) que, além de ser a forma mais prevalente entre as síndromes falciformes é, em geral, a que revela maior gravidade clínica e hematológica, tanto que seus pacientes apresentam danos orgânicos desde a infância, resultantes dos episódios vasooclusivos repetidos. 2,3Essa doença originou-se na Ásia Menor e foi trazida às Américas pelo tráfico massivo de escravos ocorrido entre o século XV e a metade do século XIX. 4 Atualmente, a AF é uma das hemoglobinopatias mais freqüentes da humanidade e representa a mais comum no Brasil, distribuindo-se de modo heterogêneo entre as diferentes regiões do país, sendo mais freqüente onde a proporção de antepassados negros da população é maior, como é o caso do Nordeste. 2Apesar de afetar cerca de 0,1% a 0,3% da população negróide brasileira, a AF é observada em parcela cada vez mais significativa da população caucasóide, em decorrência da alta taxa de miscigenação observada no Brasil. 5A falcização ou afoiçamento das hemácias, fenômeno característico da AF, além de causar anemia hemolítica crôni-

show abstract

“…This observation provided the impetus for wide-spread research efforts to understand mechanisms for ␥-gene silencing to develop strategies to reverse this process in SCD. The efficacy of Hb F is due to its ability to dilute Hb S concentrations below the threshold required for polymerization in erythrocytes; furthermore, Hb F has a direct influence on Hb S polymer stability (Bookchin et al, 1975). Asymmetric hybrid molecules Hb F/S (␣ 2 ,␥␤ S ; Bookchin et al, 1977;Nagel et al, 1979) are produced when Hb F levels remain elevated to produce the observed clinical benefit.…”

Section: Fetal Hemoglobin In Sickle Cell Diseasementioning

confidence: 99%

Understanding mechanisms of γ‐globin gene regulation to develop strategies for pharmacological fetal hemoglobin induction

Pace

Zein

2006

Developmental Dynamics

View full text Add to dashboard Cite

The developmental regulation of ␥-globin gene expression has shaped research efforts to establish therapeutic modalities for individuals affected with sickle cell disease (SCD). Fetal hemoglobin (Hb F) synthesis is high at birth, followed by a decline to adult levels by 10 months of age. The expression of ␥-globin is controlled by a developmentally regulated transcriptional program that is recapitulated during normal erythropoiesis in the adult bone marrow. It is known that naturally occurring mutations in the ␥-gene promoters cause persistent Hb F synthesis after birth, which ameliorates symptoms in SCD by inhibiting hemoglobin S polymerization and vaso-occlusion. Several pharmacological agents have been identified over the past 2 decades that reactivate ␥-gene transcription through different cellular systems. We will review the progress made in our understanding of molecular mechanisms that control ␥-globin expression and insights gained from Hb F-inducing agents that act through signal transduction pathways.

show abstract

Role of hybrid tetramer formation in gelation of haemoglobin S

Cited by 73 publications

References 9 publications

Polymerization of Three Hemoglobin A2 Variants Containing Valδ6 and Inhibition of Hemoglobin S Polymerization by Hemoglobin A2

Polymerization of Three Hemoglobin A2 Variants Containing Valδ6 and Inhibition of Hemoglobin S Polymerization by Hemoglobin A2

Importância da avaliação da hemoglobina fetal na clínica da anemia falciforme

Understanding mechanisms of γ‐globin gene regulation to develop strategies for pharmacological fetal hemoglobin induction

Contact Info

Product

Resources

About