Induction of apoptosis and of interleukin-1beta secretion by 7beta-hydroxycholesterol and 7-ketocholesterol: partial inhibition by Bcl-2 overexpression

FEBS Lett. 1997 Dec 15;419(2-3):276-80. doi: 10.1016/s0014-5793(97)01473-7.

Abstract

The oxysterols, 7beta-hydroxycholesterol and 7-ketocholesterol, are involved in the cytotoxicity of oxidized LDL. To elucidate their molecular mechanisms, the human promonocytic leukemia cells U937 and U4 were used. U4 cells overexpressing Bcl-2 were obtained by transfection of U937 cells. 7Beta-hydroxycholesterol and 7-ketocholesterol induced nuclear condensation and/or fragmentation, internucleosomal DNA fragmentation, and IL-1beta secretion, which were partially inhibited by Bcl-2 overexpression. These findings underline that these oxysterols could constitute major risk factors in atherosclerosis by their cytotoxicity and their ability to induce IL-1beta release which might favor the recruitment of immunocompetent cells in the atherosclerotic plaque.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hydroxycholesterols / pharmacology*
  • Interleukin-1 / metabolism*
  • Ketocholesterols / pharmacology*
  • Leukemia / metabolism
  • Leukemia / pathology
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Tumor Cells, Cultured

Substances

  • Hydroxycholesterols
  • Interleukin-1
  • Ketocholesterols
  • Proto-Oncogene Proteins c-bcl-2
  • cholest-5-en-3 beta,7 alpha-diol
  • 7-ketocholesterol