Electron Spin Resonance Studies of Erythrocytes from Patients with Duchenne Muscular Dystrophy

Sato, Bunzo; Nishikida, Koichi; Samuels, Leo T.; Tyler, Frank H.

doi:10.1172/jci108934

Cited by 91 publications

(45 citation statements)

References 30 publications

(29 reference statements)

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“…Fluorescence polarization studies of leukemic lymphocytes (18) and ESR studies of erythrocytes from muscular dystrophy patients (19,20) have revealed fluidity abnormalities for these formed elements of the blood. In this study we have used spin label ESR to characterize the membrane fluidity of intact, viable CHS PMN and isolated membrane fractions.…”

Section: Discussionmentioning

confidence: 99%

Membrane Fluidity in Human and Mouse Chediak-Higashi Leukocytes

et al. 1979

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A B S T R A C T Polymorphonuclear leukocytes from humans and mice with the Chediak-Higashi syndrome were characterized by spin label electron spin resonance spectrometry. Our results suggest that cells from afflicted mice and humans have membranes more fluid than controls. Order parameters for a spin label that probes near the membrane surface were 0.652 for normals and 0.645 for two Chediak-Higashi patients. Cells from Chediak-Higashi mice showed similar differences, as did isolated plasma memiibrane fractions. An increased membrane fluidity was also detected with a spin label that probes deeper in the bilayer. In vitro treatment of Chediak-Higashi mouse cells with 0.01 M ascorbate increased the order parameter to normal levels. In vitro incubation of mouse Chediak-Higashi cells with glucose oxidase increased the order parameter, similar to the effect of ascorbate. This increase was abolished when catalase was added to the incubation medium. In vitro incubation with dibutyryl cyclic guanosine monophosphate (1 ,uM to 0.1 mM) did not normalize order parameters. These results indicate that fluidity of Chediak-Higashi cell membranes was affected by treatments expected to alter the oxidation: reduction potential of the environment but was not affected by treatments expected to alter the ratio of intracellular cyclic nucleotides. The latter treatment would affect microtubule assembly. Therefore, it appears that the membrane fluidity abnormalities as demonstrated by electron spin resonance and the earlier demonstrated microtubule dysfunction s characteristic of Chediak-Higashi cells are coexistinig defects and are probably not directly related.

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Section: Discussionmentioning

confidence: 99%

Membrane Fluidity in Human and Mouse Chediak-Higashi Leukocytes

et al. 1979

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“…An increased erythrocyte membrane fluidity was observed in myotonic muscular dystrophy and congenital myotonia (8) . Abnormalities in the lateral diffusion of 5DS (43), in a lipid-protein interaction (37), and in the physical state of membrane proteins (7) have been observed in RBC membranes in Duchenne muscular dystrophy . In Huntington's disease, alterations in the physical state of erythrocyte membrane proteins (9) and in erythrocyte deformability (10) were found.…”

Section: Discussionmentioning

confidence: 99%

Fluidity properties and liquid composition of erythrocyte membranes in Chediak-Higashi syndrome.

Ingraham

Burns

Boxer

et al. 1981

The Journal of Cell Biology

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We have earlier shown through electron spin resonance (ESR) studies of leukocytes that membranes of cells from both Chediak-Higashi syndrome (CHS) mice and humans have abnormally high fluidity . We have extended our studies to erythrocytes . Erythrocytes were labeled with the nitroxide-substituted analogue of stearic acid, 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl, and ESR spectra were obtained . Order parameter, S, at 23°C, was 0.661 and 0.653 for erythrocytes of normal and CHS mice (P < 0.001) . S was 0.684 for normal human erythrocytes and 0.675 (P < 0.001) for CHS erythrocytes at 25°C. Because S varies inversely to fluidity, these results indicate that CHS erythrocytes tend to have higher fluidity than normal . In vitro treatment of both mice and human CHS erythrocytes with 10 mM ascorbate returned their membrane fluidity to normal . We prepared erythrocyte ghosts and extracted them with CHC1 3:CH3OH (2 :1) . Gas-liquid chromatography analysis showed a greater number of unsaturated fatty acids for CHS . The average number of double bonds detected in fatty acids for mice on a standard diet was 1 .77 for normal and 2.02 for CHS (P < 0.04) ; comparison of human erythrocytes from one normal control and one CHS patient showed a similar trend . Our results suggest that an increased proportion of unsaturated fatty acids may contribute to increased fluidity of CHS erythrocytes . Our observation that both leukocytes and erythrocytes of CHS have abnormal fluidity indicates that CHS pathophysiology may relate to a general membrane disorder.

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“…Furthermore, it is not possible to state whether this alteration is a primary abnormality in Ducheme muscular dystrophy or whether it might be secondary to some other disorder. For example, the proposed membrane dysfunction in Duchenne muscular dystrophy (1 I, 25,26,28,29,37,40) could lead to depletion of ATP concentrations in muscle cells. The increased consumption of ATP to maintain cellular homeostasis could accelerate purine nucleotide turnover.…”

Section: Discussionmentioning

confidence: 99%

“…Prominent hypotheses to explain the disorder have included a structural membrane abnormality (I I, 25,26,28,29,37,40) or an accelerated state of protein degradation in dystrophic muscle (16, 3 1). It is at present difficult to discern which of these possibilities may be correct or indeed, whether both types of disorders may result from a more fundamental abnormality in the dystrophic muscle cell.…”

Section: Speculationmentioning

confidence: 99%

Increased Adenine Nucleotide Turnover in Duchenne Muscular Dystrophy

Airozo

et al. 1981

Pediatr Res

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SummaryTo investigate a possible disorder of adenine nucleotide turnover in Duchenne muscular dystrophy, we evaluated 15 patients with mild Duchenne muscular dystrophy, eight patients with severe muscular dystrophy, seven patients with other neuromuscular disorders, and eight patients with hypogammaglobulinemia but no muscle disease. The serum urate concentration was similar in all four groups. Base line urinary purine excretion was elevated in all patients with neuromuscular disease with values of 1.72 & 0.15, 2.37 0.22,2.49 + 0.35, and 2.60 + 0.48 pnoles/100 ml glomerular filtration for control subjects, mild Duchenne muscular dystrophy, severe disease, and other neuromuscular diseases, respectively.Adenine nucleotide pool turnover was measured by labeling with l~14C)adenine and then 5 days later administering intravenous fructose. Five-day cumulative mean radioactivity excretion was elevated in mild and severe Duchenne muscular dystrophy with excretion values of 11.4 + 0.7 and 11.5 + 1.1% of administered radioactivity, respectively, as compared to 9.0 2 O. % of administered radioactivitv for control subiects. After intravenous fructose infusion, patients with Duchenne muscular dystrophy had a less than normal rise in serum urate concentration, a normal increase of urinary purine excretion, and a greater than normal elevation of urinary radioactivity excretion and urinary purine specific activity. Patients with other neuromuscular diseases had virtually no rise in plasma urate concentration, less than normal increase in urinary total purine excretion, and a greater than normal increase of urinary radioactivity excretion and urinary specific activity.These observations suggest that there is an increased rate of adenine nucleotide turnover in Ducheme muscular dystrophy. In patients with other neuromuscular disease an increased rate of adenine nucleotide turnover resembled the abnormality expected from a diminshed adenine nucleotide pool.

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Electron Spin Resonance Studies of Erythrocytes from Patients with Duchenne Muscular Dystrophy

Cited by 91 publications

References 30 publications

Membrane Fluidity in Human and Mouse Chediak-Higashi Leukocytes

Membrane Fluidity in Human and Mouse Chediak-Higashi Leukocytes

Fluidity properties and liquid composition of erythrocyte membranes in Chediak-Higashi syndrome.

Increased Adenine Nucleotide Turnover in Duchenne Muscular Dystrophy

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