Inositol Is Required for Red Blood Cell Integrity

Strunecká A, el Desouki NI, Palecek J, Kmonícková E, Krpejsová L, Potter BV. (1991). The effect of inositol 1,4,5-trisphosphate and inositol 1,4,5-trisphosphorothioate on calcium release and membrane skeleton organization in the human red blood cell. Receptor. 1(3):141-54.

The inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] content of unstimulated human red blood cells (RBC) has been found to be 227 +/- 83 pmol of Ins(1,4,5)P3 per mL of packed cells. Ins (1,4,5)P3 at concentrations between 0.4-5.0 microM releases Ca2+ from RBC plasma membrane with an EC50 of 0.55 microM. Inositol 4,5-bisphosphate [Ins(4,5)P2] is less potent, but inositol 1-phosphate [Ins(1)P], inositol 1,4-bisphosphate [Ins (1,4)P2], and adenosine triphosphate (ATP) are inactive. The release was stereospecific for D-Ins(1,4,5)P3; 1 microM L-Ins(1,4,5)P3 released no more Ca2+ than the control. A nonhydrolyzable analog of Ins(1,4,5)P3, inositol 1,4,5-trisphosphorothioate [Ins(1,4,5)PS3] evokes sustained release of Ca2+ from isolated ghosts. Release of 45Ca2+ was also observed after the addition of AlF4-. Ionophore A23187 and AlF4- increase the level of Ins(1,4,5)P3 in intact RBC to 1004 +/- 533 and 455 +/- 74 pmol/mL of packed RBC, respectively. We have elaborated a method for visualization of spectrin by indirect immunofluorescence in smears of RBC. Ins(1,4,5)P3 evokes shape changes in permeabilized RBC and disorganization of the spectrin network. The shape changes are stereospecific for the D-enantiomer, since L-Ins(1,4,5)P3 and other compounds had no effect. Whereas the effect of Ins(1,4,5)P3 was reversible, as was the weaker effect of Ins(4,5)P2, Ins(1,4,5)PS3 evoked irreversible shape changes. Shape changes and spectrin disorganization were also observed after the action of AlF4- and ionophore A23187. We conclude that the phosphoinositide signaling system plays an important role in the shape maintenance of human RBC.

Gersonde K, Nicolau C. (1979). Improvement of the red blood cell O2 release capacity by lipid vesicle-mediated incorporation of inositol hexaphosphate. Blut. 39(1):1-7

Fusion of unilamellar lipid vesicles with red blood cells has been used to deliver entrapped inositol hexaphosphate (IHP) to the cells. Incorporated IHP tightly bound to hemoglobin produces a significant and lasting “right-shift” of the O2-binding curve of red blood cells. The O2 release capacity of red blood cells is increased by this method up to 270% of the normal value. The Bohr effect is increased so that carbon dioxide transport is also enhanced.

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