In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2018-08-14)
Abstract:
Atropisomers with a biaryl dihydronaphthopyranone structure, dinapinones A1 (DPA1) ( M position) and A2 (DPA2) ( P position), were isolated from the fungus culture broth of Talaromyces pinophilus FKI-3864 as inhibitors of [ 14 C]neutral lipid ([ 14 C]triacylglycerol (TG) and [ 14 C]cholesteryl ester (CE)) synthesis from [ 14 C]oleic acid in Chinese hamster ovary-K1 (CHO-K1) cells. DPA2 inhibited [ 14 C]TG and [ 14 C]CE synthesis (IC 50 s , 0.65 and 5.6 μM, respectively), but DPA1 had no inhibitory activity on [ 14 C]TG and [ 14 C]CE synthesis even at 12 μM. However, a 1:1 mixture of DPA1 and DPA2 (DPA mix ) had the most potent inhibitory activity on [ 14 C]TG and [ 14 C]CE synthesis (IC 50 s, 0.054 and 0.18 μM, respectively). The mechanism of action of DPA mix was investigated. DPA mix had no effects on the enzymes involved in neutral lipid synthesis, while DPA mix enhanced the degradation of [ 14 C]neutral lipids with concomitant decrease in cytosolic lipid droplets accumulated in CHO-K1 cells. From analysis of autophagy marker proteins, DPA mix caused dose-dependent induction of microtubule-associated protein light chain 3-II (LC3-II) and degradation of p62. In the autophagic flux assay using bafilomycin A 1 , DPA mix upregulated autophagosome turnover. These results reveal that DPA mix enhances neutral lipid degradation together with induction of autophagy.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-018-30679-0
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2018
detail.hit.zdb_id:
2615211-3
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