Apolipoprotein E isoforms and their Cys ‐thiol modifications impact LRP1‐mediated metabolism of triglyceride‐rich lipoproteins

The current study offers a novel perspective on the physiological role of apolipoprotein (apo) E in lipid metabolism. The redox status of Cys-thiol in the apoE molecule significantly influences lipoprotein metabolismvia the low-density lipoprotein receptor-related protein (LRP) 1. Our findings are instrumental in understanding the pathology of various apoE-related diseases, including various atherosclerotic diseases and Alzheimer's disease. The low-density lipoprotein (LDL) receptor-related protein (LRP)1 participates in the metabolism of apolipoprotein (apo) E-containing lipoproteins (apoE-LP). We investigated the effects of modifications of cysteine (Cys)-thiol of apoE on LRP1-mediated metabolism. Among the three isoforms, apoE2-LP exhibited the lowest affinity for LRP1 but was significantly catabolized, whereas apoE4-LP was sufficiently bound to LRP1 but showed the lowest catabolic capability. The reduction enhanced the binding and suppressed the catabolism of apoE3-LP, but had no effect on apoE2-LP. The formation of disulfide-linked complexes with apoAII suppressed binding, but enhanced the catabolism of apoE2-LP. Redox modifications of apoE-Cys-thiol may modulate the LRP1-mediated metabolism of apoE2- or apoE3-LP, but not apoE4-LP. The failure of this function may be involved in the pathophysiology of dyslipidemia.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Article Source Type: research