What question did this study set out to answer?

To determine the molecular mechanism regulating PCSK9 transcription in response to sterols and evaluate the specific involvement of SREBP-1 and SREBP-2.

October 6, 2007Journal of Lipid ResearchOpen Access

Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2

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Authors

HJHyun Jeong JeongYonsei University HLHyun‐Sook LeeChungnam National University KKKyung‐Sup KimYonsei University

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Implication

Laboratory and mouse study demonstrates sterol-dependent transcriptional regulation of PCSK9 via SREBP-2 in hepatocytes, indicating a direct feedback loop in cholesterol homeostasis.

Key Points

To determine the molecular mechanism regulating PCSK9 transcription in response to sterols and evaluate the specific involvement of SREBP-1 and SREBP-2.
Assessed PCSK9 promoter activity, sterol responsiveness, and protein-DNA interactions using promoter-reporter assays and in vitro binding with human HepG2 cells.
Analyzed hepatic Pcsk9 mRNA, Pcsk9 protein, and nuclear Srebp-2 levels in mice under fasting, refeeding, and 2% cholesterol dietary conditions.
PCSK9 promoter activity in HepG2 cells depended on a sterol-regulatory element (SRE), and binding of nuclear SREBP-1 and SREBP-2 robustly induced transcription in vitro.
Hepatic Pcsk9 mRNA and protein decreased during fasting and increased upon refeeding in mice, but supplementation with a 2% cholesterol diet completely prevented the refeeding-induced increase.
Refeeding-induced changes in mouse liver Pcsk9 mRNA correlated with nuclear Srebp-2 levels, demonstrating that SREBP-2 mediates the sterol-dependent regulation of PCSK9 in vivo.

Cite This Study

Jeong et al. (2007) studied this question.

synapsesocial.com/papers/69dcffbde3a90a2e2f133657 https://doi.org/10.1194/jlr.m700443-jlr200

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Implication

Laboratory and mouse study demonstrates sterol-dependent transcriptional regulation of PCSK9 via SREBP-2 in hepatocytes, indicating a direct feedback loop in cholesterol homeostasis.

Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2

Discussion

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Implication

Key Points

Cite This Study

Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2

Discussion

Member takes

Implication

Key Points

Cite This Study

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