Effect of curcumin on amyloid‐like aggregates generated from methionine‐oxidized apolipoprotein A‐I

Abstract

Curcumin is a polyphenolic phytonutrient that has antineurodegenerative properties. In this study, we investigated the anti‐amyloidogenic properties of curcumin. Following incubation with curcumin, intrinsic tryptophan fluorescence emission of apolipoprotein (apo) A‐I was strongly quenched. At the same time, curcumin fluorescence emission was enhanced. The fluorescence emission spectra of curcumin in the presence of amyloid‐like aggregates formed by methionine‐oxidized (ox) apoA‐I varied, depending on whether curcumin was added before, or after, aggregate formation. The impact of curcumin on the structure of the aggregating material was revealed by the lower amount of β‐structure in ox‐apoA‐I amyloid‐like aggregates formed in the presence of curcumin, compared to aggregates formed without curcumin. However, the kinetics of ox‐apoA‐I amyloid‐like aggregate formation was not altered by the presence of curcumin. Moreover, electron microscopy analysis detected no discernable differences in amyloid morphology when ox‐apoA‐I amyloid‐like aggregates were formed in the presence or absence of curcumin. In conclusion, curcumin interacts with apoA‐I and alters the structure of ox‐apoA‐I amyloid‐like aggregates yet does not diminish the propensity of ox‐apoA‐I to form aggregates.

Renal expression of JAK2 is high in polycystic kidney disease and its inhibition reduces cystogenesis

“…4B ). Previous studies have suggested that curcumin can cause protein precipitation into aggresomes 29 , 30 , we therefore suggest that these punctate structures may be JAK2 aggregates. This could explain how JAK2 becomes insoluble and provide an explanation as to why we were unable to detect JAK2 in the detergent-soluble fraction by immunoblotting.…”

“…Curcumin causes JAK2 to move into an insoluble fraction, and we observe the generation of large JAK2 positive puncta in cells treated with curcumin. We do not know the nature of these puncta, however, curcumin has been previously shown to cause protein aggregation 29 , therefore we propose that these structures may be aggresomes. The observation that these JAK2 positive puncta are not dependent on proteasomal processing of JAK2 is evidence that JAK2 has not been degraded.…”

JAK2 is highly expressed by cyst-lining cells and regulates cystogenesis

“…4B). Previous studies have suggested that curcumin can cause protein precipitation into aggresomes 22,23 , we therefore suggest that these punctate structures are JAK2 aggregates. This explains indicates that JAK2 become insoluble and therefore explains why we were unable to detect JAK2 in the detergent-soluble fraction by immunoblotting.…”

“…Curcumin has previously been shown to cause precipitation of proteins into aggresomes (19,20). To test whether JAK2 was moved into an insoluble aggregated state, we next performed immunocytochemistry in cells treated either with DMSO control or 1, 3 or 6 hours treatment with 50 μM of curcumin.…”

“…Curcumin has been shown to be neuroprotective, by preserving gross intramolecular conformation of beta amyloids, while disrupting the intermolecular arrangements, a phenomenon which is very similar to the effects of Zn 2+ ions, as reported previously (17). Likewise, curcumin can alter the structure of lipoproteins by interacting with the soluble intermediates, thus altering their aggregation patterns (16). Similarly, A20, which is an anti-inflammatory zinc-finger protein is shown to cause aggregation of NFκB (an inflammatory transcription factor) and mediate vascular protection (28).…”