DITHIOTHREITOL STIMULATES THE ACTIVITY OF THE PLASMA-MEMBRANE AMINOPHOSPHOLIPID TRANSLOCATOR

Metabolic depletion induces human erythrocytes to crenate, a shape cha nge that is reversed when ATP is regenerated by nutrient supplementati on. In the presence of the sulfhydryl reducing agent dithiothreitol (D TT), this shape reversal is exaggerated, proceeding beyond normal disc oid morphology to stomatocytic forms. DTT-induced stomatocytosis does not correlate consistently with alterations in cell ATP, spectrin phos phorylation, or phosphoinositide metabolism (Truong, H.-T.N., Ferrell, J.E., Jr. and Huestis, W.H. (1986) Blood 67, 214-221). The effect of DTT on outer-to-inner-monolayer transport of aminophospholipids was ex amined by monitoring shape changes induced by dilauroylphosphatidylser ine (DLPS). Stomatocytosis induced by transport of this exogenous lipi d to the membrane inner monolayer is accelerated and exaggerated by DT T. The effect of DTT on DLPS translocation is reversible and temperatu re dependent, consistent with the intervention of reducing agents in t he activity of the aminophospholipid translocator. These findings bear on the relationship between cell redox status and shape regulation.