Changes in expression of antioxidant enzymes affect cell-mediated LDL oxidation and oxidized LDL-induced apoptosis in mouse aortic cells.
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 Gpx1(-/-) mice. CuSO(4)-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.
Guo
Z
Z
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. GUO@uthscsa.edu
Van Remmen
H
H
Yang
H
H
Chen
X
X
Mele
J
J
Vijg
J
J
Epstein
C J
CJ
Ho
Y S
YS
Richardson
A
A
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000166:cytology* / Q000201:enzymology*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D046508:Culture Techniques; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008077:Lipoproteins, LDL / Q000096:biosynthesis* / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000094765:Glutathione Peroxidase GPX1
D000975:Antioxidants; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D020169:Caspases; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse