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| Apoptosis caused by oxidized LDL is manganese superoxide dismutase and p53 dependent |
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| Author(s): Kinscherf R, Claus R, Wagner M, Gehrke C, Kamencic H, Hou D, Nauen O, Schmiedt W, Kovacs G, Pill J, Metz J, Deigner HP |
| Source: FASEB JOURNAL Volume: 12 Issue: 6 Pages: 461-467 Published: APR 1998 |
| Times Cited: 94 References: 52 |
| Abstract: Oxidized low density lipoprotein (oxLDL) induces apoptosis in human macrophages (M Phi), a significant feature in atherogenesis. We found that induction of apoptosis in M Phi by oxLDL, C-2-ceramide, tumor necrosis factor alpha (TNF-alpha), and hydrogen peroxide (H2O2) was associated with enhanced expression of manganese superoxide dismutase (MnSOD) and p53. Treatment of cells with p53 or MnSOD antisense oligonucleotides prior to stimulation with oxLDL, C-2-ceramide, TNF-alpha, or H2O2 caused an inhibition of the expression of the respective protein together with a marked reduction of apoptosis. Exposure to N-acetylcysteine before treatment with oxLDL, C-2-ceramide, TNF-alpha, or H2O2 reversed a decrease in cellular glutathione concentrations as well as the enhanced production of p53 and MnSOD mRNA and protein. In apoptotic macrophages of human atherosclerotic plaques, colocalization of MnSOD and p53 immunoreactivity was found. These results indicate that in oxLDL-induced apoptosis, a concomitant induction of p53 and MnSOD is critical, and suggest that it is at least in part due to an enhancement of the sphingomyelin/ceramide pathway. |
| Document Type: Article |
| Language: English |
| Reprint Address: Deigner, HP (reprint author), Univ Heidelberg, Inst Pharmaceut Chem, Neuenheimer Feld 364, D-69120 Heidelberg, Germany |
Addresses:
1. Univ Heidelberg, Inst Pharmaceut Chem, D-69120 Heidelberg, Germany
2. Univ Heidelberg, Dept Anat & Cell Biol 3, D-69120 Heidelberg, Germany
3. Univ Heidelberg, Dept Urol, D-69120 Heidelberg, Germany
4. Dept Cardiothorac & Vasc Surg, D-55101 Mainz, Germany
5. Boehringer Mannheim, Dept Preclin Res, D-68298 Mannheim, Germany |
| Publisher: FEDERATION AMER SOC EXP BIOL, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA |
| Subject Category: Biochemistry & Molecular Biology; Biology; Cell Biology |
| IDS Number: ZG118 |
| ISSN: 0892-6638 |
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