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Hydrogen sulfide inhibits PCSK9 expression through the PI3K/Akt‑SREBP‑2 signaling pathway to influence lipid metabolism in HepG2 cells.
- Source :
-
International journal of molecular medicine [Int J Mol Med] 2019 May; Vol. 43 (5), pp. 2055-2063. Date of Electronic Publication: 2019 Mar 01. - Publication Year :
- 2019
-
Abstract
- Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule that plays important roles in the cardiovascular system. In our previous studies, we demonstrated that H2S regulates lipid metabolism. In the present study, we aimed to explore the mechanisms through which H2S regulates lipid metabolism in HepG2 cells in vitro. Treatment of the HepG2 cells with H2S inhibited the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and increased the level of low‑density lipoprotein receptor (LDLR) in a time‑ and dose‑dependent manner. The knockdown of PCSK9 by siRNA effectively increased the levels of LDLR and 1,1'‑dioctadecyl‑3,3,3',3'‑tetramethyl‑indocarbocyanine perchlorate‑labeled LDL (DiI‑LDL) uptake in the H2S‑treated HepG2 cells. Furthermore, the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt)‑sterol regulatory element binding proteins 2 (SREBP‑2) signaling pathway was confirmed to be involved in H2S‑regulated PCSK9 expression. Notably, the HepG2 cells were incubated with 30% serum and DiI‑LDL for 24 h, and the results revealed that H2S increased lipid uptake, but caused no increase in lipid accumulation. On the whole, the findings of this study demonstrate that H2S is involved in the regulation of lipid metabolism in HepG2 cells through the regulation of the expression of PCSK9 via the PI3K/Akt‑SREBP‑2 signaling pathway. To the very best of our knowledge, this study is the first to report that H2S can regulate the expression of PCSK9.
- Subjects :
- Hep G2 Cells
Humans
Models, Biological
Proprotein Convertase 9 metabolism
Receptors, LDL metabolism
Up-Regulation drug effects
Hydrogen Sulfide pharmacology
Lipid Metabolism drug effects
PCSK9 Inhibitors
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction drug effects
Sterol Regulatory Element Binding Protein 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-244X
- Volume :
- 43
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30864739
- Full Text :
- https://doi.org/10.3892/ijmm.2019.4118