Redox index of Cys-thiol residues of serum apolipoprotein E and its diagnostic potential.

BACKGROUND

The redox modulation of Cys-thiol participates in various pathophysiological processes. We explored the proper index for estimating the redox status of Cys-thiol of serum apolipoprotein E (apoE), named "redox-IDX-apoE," which is necessary to understand the redox biology of age-related diseases.

METHODS

The fractions of the reduced form (red-), reversible oxidized form (roxi-), and irreversibly oxidized form (oxi-) apoE in serum, obtained from the patients with no apparent disease (controls, n=192) and with atherosclerosis and type 2 diabetes (patients, n=16), were measured by a band-shift assay using a maleimide compound. Redox-IDX-apoE candidates were determined by calculating the values of these fractions and the total apoE concentration.

RESULTS

Cys number of apoE significantly increased for the ratio of roxi-apoE to total-apoE (roxi/total) (E2/E3>E3/E3>E3/E4) but decreased for the ratios of red-apoE to roxi-apoE (red/roxi) and [red-apoE + oxi-apoE] to roxi-apoE ([red + oxi]/roxi) (E2/E3<E3/E3<E3/E4). Considering the subjects with apoE3/E3, these ratios were independent of age and sex. Roxi/total showed negative correlations with serum triglyceride (TG) and HbA1c levels, while both red/roxi and [red + oxi]/roxi showed significant positive correlations with them. However, red/roxi and [red + oxi]/roxi in patients were significantly lower than those in controls, although serum TG and HbA1c levels in the patients were significantly higher than those in controls.

CONCLUSION

The redox status of serum apoE-Cys-thiol is closely involved in the metabolism of TG-rich lipoproteins and glucose. The appropriate use of redox-IDX-apoE could be helpful in the diagnosis and prognosis of age-related diseases and in understanding the underlying mechanisms.