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.
|Number of pages
|Arteriosclerosis, thrombosis, and vascular biology
|Published - 2001
- Antioxidant enzymes
- Transgenic mice
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine