Enhanced secretion of ApoB by transfected HepG2 cells overexpressing fibrinogen

Biochem Biophys Res Commun. 2000 Jun 24;273(1):377-84. doi: 10.1006/bbrc.2000.2914.

Abstract

HepG2 cells stably transfected with cDNA-encoding single fibrinogen chains overexpress fibrinogen and have increased (4-fold) secretion of apolipoprotein B. Overexpression of fibrinogen does not affect the secretion of three representative acute-phase proteins but causes a small increase in albumin secretion. Enhanced apolipoprotein B secretion is due to less intracellular degradation and not to increased expression. The increased secretion of apolipoprotein B is independent of the acute-phase response, since stimulation of fibrinogen gene expression by interleukin 6 did not affect secretion. HepG2 cells overexpressing fibrinogen chains had increased 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels, enhanced cholesterol production but normal levels of triglyceride and phospholipid synthesis and of sterol response binding proteins. These results, that associate overexpression of fibrinogen with enhance apolipoprotein B secretion, may be significant since epidemiological studies indicate that elevated levels of fibrinogen and lipids are independent risk factors in coronary artery disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Acute-Phase Reaction
  • Albumins / metabolism
  • Apolipoproteins B / biosynthesis
  • Apolipoproteins B / genetics
  • Apolipoproteins B / metabolism*
  • Cholesterol / biosynthesis
  • Cysteine Proteinase Inhibitors / pharmacology
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / analysis
  • Fibrinogen / biosynthesis
  • Fibrinogen / genetics
  • Fibrinogen / metabolism*
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Interleukin-6 / pharmacology
  • Leupeptins / pharmacology
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Phospholipids / analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Response Elements / genetics
  • Sterols / metabolism
  • Transfection
  • Triglycerides / analysis
  • Tumor Cells, Cultured

Substances

  • Acute-Phase Proteins
  • Albumins
  • Apolipoproteins B
  • Cysteine Proteinase Inhibitors
  • DNA, Complementary
  • DNA-Binding Proteins
  • Interleukin-6
  • Leupeptins
  • Phospholipids
  • RNA, Messenger
  • Sterols
  • Triglycerides
  • Fibrinogen
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde