Diabetes, Vol 40, Issue 6 701-708, Copyright © 1991 by American Diabetes Association

ARTICLES

Oxidation of spectrin and deformability defects in diabetic erythrocytes

RS Schwartz, JW Madsen, AC Rybicki and RL Nagel
Albert Einstein College of Medicine/Montefiore Medical Center, Division of Hematology, Bronx, New York 10467.

We reasoned that de novo oxidative damage, as a result of increased protein glycosylation, could participate in the mechanisms whereby diabetic erythrocytes acquire membrane abnormalities. To examine this hypothesis, the extent of erythrocyte membrane protein glycosylation and the oxidative status of spectrin, the major component of the erythrocyte membrane skeleton, were examined. Labeling erythrocyte membranes with [3H]borohydride, which labels glucose residues bound to proteins, revealed that several proteins were heavily glycosylated compared with nondiabetic erythrocyte membranes. In particular, the proteins beta-spectrin, ankyrin, and protein 4.2 were the most glycosylated. Although sodium dodecyl sulfate-polyacrylamide gel electrophoresis of diabetic erythrocyte membranes did not reveal any quantitative or qualitative abnormalities in spectrin or other membrane proteins, examination of spectrin oxidative status by amino acid analysis and with cis-dichlorodiammineplatinum(II) (cDDP), a chemical probe specific for protein methionine and cysteine residues, demonstrated that the diabetic spectrin was oxidatively damaged: spectrin from diabetic subjects contained 35% less methionine (P less than 0.002), 15% less histidine (P less than 0.006), and a twofold increase in cysteic acid (P less than 0.001) compared with normal spectrin. Diabetic spectrin bound 32% less cDDP than normal spectrin (P less than 0.001); the lowest cDDP binding was observed with spectrin from insulin-dependent diabetic subjects. The extent of cDDP binding to diabetic spectrin correlated moderately and inversely with glycosylated hemoglobin (GHb) levels (n = 12, r = -0.727). Erythrocyte deformability, measured by ektacytometry, was decreased between 5 and 23% of control measurements (average of approximately 10%) in 21 of 32 diabetic subjects surveyed.(ABSTRACT TRUNCATED AT 250 WORDS)
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