NK-104, a potent new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, enhances posttranslational catabolism of apolipoprotein B-100 and inhibits secretion of apolipoprotein B-100 and triacylglycerols from HepG2 cells

Teruyoshi Yanagita, Emi Hara, Hiroaki Yotsumoto, Shaikh M. Rahman, Sco Y. Han, Jae Young Cha, Kyosuke Yamamoto

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The effects of NK-104, a new, potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the secretion and intracellular catabolism of apolipoprotein B-100 (apo) and on lipid metabolism in HepG2 cells were investigated. The cells were treated with NK-104 1 or 10 μM for 3 or 24 hours in 1% bovine serum albumin-containing medium. To examine intracellular apo B catabolism, the cells were labeled with 35S-methionine for 10 minutes and followed for up to 90 minutes. NK-104 reduced the secretion of apo B and 35S-labeled apo B. The degradation rate of intracellular 35S-labeled apo B was faster in cells treated with NK-104 than in controls, suggesting that apo B stability was decreased by treatment with NK-104, NK-104 reduced significantly the intracellular levels and synthesis of cholesterol and cholesteryl ester in HepG2 cells. The agent reduced the secretion of labeled triacylglycerols without affecting intracellular triacylglycerol synthesis. Results of this study suggest that NK-104 reduced the secretion of apo B by enhancing degradation of the protein. This effect may be mediated through changes in the intracellular metabolism of cholesterol or cholesteryl ester.

Original languageEnglish
Pages (from-to)423-434
Number of pages12
JournalCurrent Therapeutic Research - Clinical and Experimental
Volume60
Issue number8
DOIs
StatePublished - 1999

Keywords

  • Apo B degradation
  • Apo B secretion
  • Cholesteryl ester
  • HMG-CoA reductase inhibitor
  • HepG2 cells
  • Triacylglycerol

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