Changes in expression of antioxidant enzymes affect cell-mediated LDL oxidation and oxidized LDL-induced apoptosis in mouse aortic cells

Zhong Mao Guo, Holly Van Remmen, Hong Yang, Xin Lian Chen, James Mele, Jan Vijg, Charles J. Epstein, Ye Shih Ho, Arlan Richardson

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Transgenic mice overexpressing Cu/Zn superoxide dismutase (hSod1Tg+/0) or catalase (hCatTg+/0) and knockout mice underexpressing manganese superoxide dismutase (Sod2+/-) or glutathione peroxidase-1 (Gpx1-/-) were used to study the effect of antioxidant enzymes on cell-mediated low density lipoprotein (LDL) oxidation and oxidized LDL (oxLDL)-induced apoptosis. Incubation of LDL with mouse aortic segments or smooth muscle cells (SMCs) resulted in a significant increase in LDL oxidation. However, LDL oxidation was significantly reduced when LDL was incubated with aortic segments and SMCs obtained from hSod1Tg+/0 and hCatTg+/0 mice compared with those obtained from wild-type mice. In contrast, LDL oxidation was significantly increased when LDL was incubated with aortic segments and SMCs obtained from Sod2+/- and Gpxl-/- mice. CuSO4-oxidized LDL increased DNA fragmentation and caspase activities in the primary cultures of mouse aortic SMCs. However, oxLDL-induced DNA fragmentation and caspase activities were reduced 50% in SMCs obtained from hSod1Tg+/0 and hCatTg+/0 mice compared with wild-type control mice. In contrast, oxLDL-induced DNA fragmentation and caspase activities were significantly increased in SMCs obtained from Sod2+/- and Gpx1-/- mice. These findings suggest that overexpression of Cu/Zn superoxide dismutase or catalase reduces cell-mediated LDL oxidation and oxLDL-induced apoptosis, whereas underexpression of manganese superoxide dismutase or glutathione peroxidase-1 increases cell-mediated LDL oxidation and oxLDL-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)1131-1138
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume21
Issue number7
DOIs
Publication statusPublished - Jan 1 2001
Externally publishedYes

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Keywords

  • Antioxidant enzymes
  • Aortas
  • LDL
  • Transgenic mice

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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