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.