Journal
ACS OMEGA
Volume 5, Issue 48, Pages 31126-31136Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsomega.0c04282
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Funding
- National Research Foundation of Korea (NRF) - Korean government (MSIT), Republic of Korea [NRF-2019R1A2C2009053, NRF-2018R1A5A2023127]
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Whole-transcriptome analysis of alpha-mangostin-treated HepG2 cells revealed that genes relevant to lipid and cholesterol metabolic processes responded to alpha-mangostin treatment. alpha-Mangostin downregulated a series of cholesterol biosynthetic genes, including SQLE, HMGCR, and LSS, and controlled specific cholesterol trafficking-associated genes such as ABCAI, SOATI, and PCSK9. In particular, the downregulation of SREBP2 expression highlighted SREBP2 as a key transcriptional factor controlling lipid or cholesterol metabolic processes. Gene network analysis of SREBP2 and responses of its target proteins demonstrated that the effect of a-mangostin on HepG2 cells was mediated by the downregulation of SREBP2 expression, which was further supported by the reduction of the amount of SREBP2-SCAP complex. In the presence of exogenous cholesterols, alpha-mangostin downregulated SREBP2 expression and suppressed PCSK9 synthesis, which might contribute to the increased cholesterol uptake in cells, in part explaining the cholesterol-lowering effect of alpha-mangostin.
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