Knockdown of apolipoprotein B, an atherogenic apolipoprotein, in HepG2 cells by lentivirus-mediated siRNA.

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  • Author(s): Liao W;Liao W; Ning G
  • Source:
    Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2006 Jun 02; Vol. 344 (2), pp. 478-83. Date of Electronic Publication: 2006 Apr 04.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-291X (Print) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Gene Silencing*; Apolipoproteins B/*genetics ; Apolipoproteins B/*metabolism ; Hepatocytes/*metabolism ; Hepatocytes/*pathology ; Lentivirus/*genetics ; RNA, Small Interfering/*genetics; Atherosclerosis/metabolism ; Cell Line ; Endoplasmic Reticulum Chaperone BiP ; Gene Targeting/methods ; Genetic Therapy/methods ; Humans ; RNA, Small Interfering/administration & dosage ; Transfection/methods
    • Abstract:
      ApoB is an important determinant of atherosclerosis susceptibility and a potential pharmaceutical target for lowering atherogenic lipoproteins. In the present study, we used a lentiviral vector to express short hairpin RNAs for inhibition of apoB production in HepG2 cells. We first demonstrated that lentivirus could efficiently deliver transgene into HepG2 cells by using GFP lentivirus. We then made three lentiviral siApoB constructs, two of which were highly efficient for silencing apoB expression in HepG2 cells. We showed that siApoB lentivirus specifically knocked down apoB but had no effects on other proteins such as apoAI and albumin. Consequently, the secretion of apoB was reduced markedly. The silencing effect of siApoB lentivirus appeared to be permanent. Knocking down apoB did not alter the expression of cytoplasmic stress proteins (HSP70 and HSP90) and their ER homologues (GRP78 and GRP94). Furthermore, neither IKKalpha and JNK nor phosphorylated IKK and JNK were increased in long-term apoB-deficient hepatocytes as compared to the control cells. Consistent with these findings, apoB-deficient hepatocytes responded to insulin to a similar extent as the control cells as determined by measuring insulin-induced phosphorylation of IRS and ERK. Our studies indicate that lentiviral siRNAs provide an excellent approach for delivering siRNA into HepG2 cells and may be used for gene therapy for hyperlipidemia.
    • Accession Number:
      0 (Apolipoproteins B)
      0 (Endoplasmic Reticulum Chaperone BiP)
      0 (HSPA5 protein, human)
      0 (RNA, Small Interfering)
    • Publication Date:
      Date Created: 20060420 Date Completed: 20060622 Latest Revision: 20211203
    • Publication Date:
      20221213
    • Accession Number:
      10.1016/j.bbrc.2006.03.164
    • Accession Number:
      16620782