The Heme and Sickle Cell Hemoglobin Polymerization

Intracellular polymerization of sickle hemoglobin. Effects of cell heterogeneity.

To determine the extent to which the broad distribution in intracellular hemoglobin concentrations found in sickle erythrocytes affects the extent of intracellular polymerization of hemoglobin S, we have fractionated these cells by density using discontinuous Stractan gradients. The amount of polymer formed in the subpopulations was experimentally measured as a function of oxygen saturation usi...

The intracellular polymerization of sickle hemoglobin and its relevance to sickle cell disease.

In the last few years. the understanding of the molecular basis of sickle cell disease has progressed rapidly. It is now possible to describe the structure of the gel of polymerized deoxyhemoglobin S at molecular and atomic levels and to begin to understand the mechanism of formation of this gel from hemoglobin solutions. There are several current hypotheses for the pathophysiology of this dise...

Beyond hemoglobin polymerization: the red blood cell membrane and sickle disease pathophysiology.

Variation in fetal hemoglobin parameters and predicted hemoglobin S polymerization in sickle cell children in the first two years of life: Parisian Prospective Study on Sickle Cell Disease.

Intracellular hemoglobin S (HbS) polymerization is most likely to be the primary determinant of the clinical and biologic manifestations of sickle cell disease (SCD). Fetal hemoglobin (HbF) does not enter the HbS polymer and its intracellular expression in sickle erythrocytes inhibits polymerization. HbF levels, high at birth but decreasing thereafter, protect the newborn from the clinical mani...

Dimethyl fumarate increases fetal hemoglobin, provides heme detoxification, and corrects anemia in sickle cell disease.

Sickle cell disease (SCD) results from a point mutation in the β-globin gene forming hemoglobin S (HbS), which polymerizes in deoxygenated erythrocytes, triggering recurrent painful vaso-occlusive crises and chronic hemolytic anemia. Reactivation of fetal Hb (HbF) expression ameliorates these symptoms of SCD. Nuclear factor (erythroid derived-2)-like 2 (Nrf2) is a transcription factor that trig...