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

ZhongMao Guo, Holly Van Remmen, Hong Yang, XinLian Chen, James Mele, Jan Vijg, Charles J. Epstein, Ye Shih Ho, Arlan Richardson

Research output: Contribution to journalArticle

76 Citations (Scopus)

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
StatePublished - 2001

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LDL Lipoproteins
Antioxidants
Apoptosis
Smooth Muscle Myocytes
Enzymes
DNA Fragmentation
Caspases
Catalase
Superoxide Dismutase
oxidized low density lipoprotein
Knockout Mice
Transgenic Mice

Keywords

  • Antioxidant enzymes
  • Aortas
  • LDL
  • Transgenic mice

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Changes in expression of antioxidant enzymes affect cell-mediated LDL oxidation and oxidized LDL-induced apoptosis in mouse aortic cells. / Guo, ZhongMao; Van Remmen, Holly; Yang, Hong; Chen, XinLian; Mele, James; Vijg, Jan; Epstein, Charles J.; Ho, Ye Shih; Richardson, Arlan.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 21, No. 7, 2001, p. 1131-1138.

Research output: Contribution to journalArticle

Guo, Z, Van Remmen, H, Yang, H, Chen, X, Mele, J, Vijg, J, Epstein, CJ, Ho, YS & Richardson, A 2001, 'Changes in expression of antioxidant enzymes affect cell-mediated LDL oxidation and oxidized LDL-induced apoptosis in mouse aortic cells', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 21, no. 7, pp. 1131-1138.
Guo, ZhongMao ; Van Remmen, Holly ; Yang, Hong ; Chen, XinLian ; Mele, James ; Vijg, Jan ; Epstein, Charles J. ; Ho, Ye Shih ; Richardson, Arlan. / Changes in expression of antioxidant enzymes affect cell-mediated LDL oxidation and oxidized LDL-induced apoptosis in mouse aortic cells. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2001 ; Vol. 21, No. 7. pp. 1131-1138.
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AU - Mele, James

AU - Vijg, Jan

AU - Epstein, Charles J.

AU - Ho, Ye Shih

AU - Richardson, Arlan

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AB - 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.

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