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 language | English (US) |
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Pages (from-to) | 1131-1138 |
Number of pages | 8 |
Journal | Arteriosclerosis, thrombosis, and vascular biology |
Volume | 21 |
Issue number | 7 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
Keywords
- Antioxidant enzymes
- Aortas
- LDL
- Transgenic mice
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine