Stabilization of small heterodimer partner mRNA by grape seed procyanidins extract in cultured hepatocytes

Abstract

Consumption of dietary grape seed procyanidins extract (GSPE) has improved the plasma lipid profile in humans and experimental animals. The effect of GSPE on the reduction of the postprandial plasma triglyceride (TG) levels has been attributed to the activation of the small heterodimer partner (SHP). GSPE increases SHP gene expression in rat liver and the TG-lowering effect of GSPE is abolished in SHP-deficient mice. However, the mechanism by which GSPE increases SHP mRNA levels remains unclear. This study addressed the effect of GSPE on SHP mRNA stability. The present study shows for the first time that SHP mRNA is rapidly degraded, as measured by actinomycin D-based mRNA chase experiments, and GSPE transiently stabilizes SHP mRNA in HepG2 cells. This degradative effect was completely abolished with 2 h of prolonged treatment with GSPE. However, treatment of fresh HepG2 cells with a pretreated GSPE-containing medium also stabilized SHP mRNA, indicating that GSPE inactivation is not responsible for the transient effects that GSPE has on SHP mRNA stability. SHP expression is intricately controlled by mRNA stabilization, which is transiently increased by GSPE, along with at the transcriptional and posttranslational levels.