Transcriptional suppression of human apolipoproteina4 and apolipoproteinc3 genes by phorbol myristate acetate in hepatic and intestinal cells
Issue title: Frontiers in Biomedical Engineering and Biotechnology – Proceedings of the 2nd International Conference on Biomedical Engineering and Biotechnology, 11–13 October 2013, Wuhan, China
Affiliations: Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin, University, Changchun, China | First Hospital of Jilin Chemical Group Corporation, General Hospital, Jilin, China | The First Hospital of Jilin University, Changchun, China | The Second Hospital of Jilin University, Changchun, China | Norman Bethune College of Medicine, Jilin University, Changchun, China
Note: [] These authors contributed equally to this work.
Note: [] These authors contributed equally to this work.
Note: [] Correspondence to: Dr. Ronggui Li, Tel.: 86-431 85619481; Fax: 86-431-85619469; E-mail: [email protected]
Note: [] Correspondence to: Dr. Zonggui Wang, Tel.: 86-431 88796114; E-mail: [email protected]
Abstract: Background: Genetic, epidemiological and clinical evidence has demonstrated the importance of the human apolipoproteinA5 (apoA5), apolipoproteinA4 (apoA4), apolipoproteinC3 (apoC3), and apolipoproteinA1 (apoA1) genes in the control of the triglyceride and cholesterol concentrations in the blood. However, little is known about the mechanism by which protein kinase C (PKC) regulates the expression of these genes in hepatic and intestinal cells. The aim of this study was to explore the regulatory role of PKC on the expression of apoA5, apoA4, apoC3 and apoA1. Methods: Hepatic HepG2 and intestinal Caco-2 cells were treated with a potent PKC activator, Phorbol myristate acetate (PMA). The real time quantitative RT-PCR (qRT-PCR) technique was used to evaluate the effects of PMA on the expression of apoA1, apoA4, apoA5 and apoC3 genes. Nuclear run on assay was used to determine whether the effect of PMA on apoA4 and apoC3 was due to its ability to regulate the transcription of these genes. Results: PMA specifically down-regulated the transcription of apoA4 and apoC3, but exhibited no effects on apoA1 or apoA5 in either HepG2 or Caco-2 cells. Further study by nuclear run on assay proved that the suppressive effect of PMA on apoA4 and apoC3 resulted from PMA's regulation of the transcription rate of the two genes. Conclusions: PMA down-regulated transcription of apoA4 and apoC3 possibly through the common regulatory element shared by these two genes, suggesting a suppressive role of PKC on the transcriptional regulation of specific apolipoproteins in hepatic and intestinal cells.
