Abstract 127: Differential Role of Quercetin Treatment on MicroRNA Signaling and Lipid Metabolism in HepG2 Cells Exposed to 13-HPODE
Background: Quercetin is a member of the bioflavonoids family known to have antiatherogenic, antiinflammatory, and antihypertensive properties; and reported to have cardiovascular protective role. Quercetin through its antioxidant action may protect against oxidative stress induced by free radicals consequently decreasing the potential for modification of low density lipoprotein cholesterol (LDL). Members of a class of non-coding RNAs termed microRNAs have recently been identified to be potent post-transcriptional regulators of lipid metabolism genes, including cholesterol homeostasis. Data from our ongoing study on mice have demonstrated that quercetin mediates lipoprotein gene expression and host of MicroRNAs impacting plasma lipoprotein levels.
Aims and Objectives: The goal of this study is to investigate the beneficial protective effect of Quercetin on HepG2 cell line subjected to the treatment of 13-HPODE an oxidatively modified linoleic acid derivative, and also to investigate the effects of treatments on specific group of MicroRNAs.
Study Design and Methods: We treated HepG2 cell line with two different Quercetin concentrations: 20 and 40 μmoles in the presence or absence of 13-HPODE an oxidizing agent or Linoleic acid as control. After 12 and 24 hours of treatments, RNAs from treated cells were extracted and gene expressions in the various conditions were performed for selected lipoproteins genes specifically APOA1, ApoC3, APOA5, PPAR-alpha, NPCL1, and ABCA1 examining the protective role of Quercetin against 13-HPODE treated HepG2 cells. In addition we investigated role of quercetin and 13-HPODE on MicroRNAs 21, 29a,155 and 451 In addition; serum deprived mediums were collected and markers of oxidative stress and inflammations, PON1, TNF-alpha, and MCP1 were analyzed using commercially available ELISA kits.
Results and Discussion: Our data excitingly shows that Quercetin differentially influences the levels of lipoprotein gene expression, MicroRNAs and oxidative stress and inflammatory markers in HepG2 cells and the medium. Interestingly Quercetin seems to down regulate ApoC3 mRNA expression, and differentially affects ApoA1 and ApoA5 genes and MicroRNA levels. Serum deprived cells TNF-alpha levels seem to follow the prototype shown by the cellular changes, we also did not see dose dependant responses in any of the treatments.
Conclusion: Liver cells are responsible for a major part of lipoprotein metabolism, however our studies using HepG2 cells have demonstrated that Quercetin although is known for its antioxidant properties, did not seems to have dose dependant responses to modulate the oxidative stress induced by 13-HPODE and differentially affect the levels of lipoprotein gene expression.
- © 2012 by American Heart Association, Inc.