Faculty Collaboration Database

Inhibition of oxidized low-density lipoprotein-induced apoptosis in endothelial cells by nitric oxide. Peroxyl radical scavenging as an antiapoptotic mechanism. J Biol Chem 2001 May 18;276(20):17316-23

Date

03/30/2001

Pubmed ID

11278975

DOI

10.1074/jbc.M011731200

Scopus ID

2-s2.0-0035907359 (requires institutional sign-in at Scopus site)   66 Citations

Abstract

Proatherogenic oxidized low-density lipoprotein (oxLDL) induces endothelial apoptosis. We investigated the anti-apoptotic effects of intracellular and extracellular nitric oxide (*NO) donors, iron chelators, cell-permeable superoxide dismutase (SOD), glutathione peroxidase mimetics, and nitrone spin traps. Peroxynitrite (ONOO-)-modified oxLDL induced endothelial apoptosis was measured by DNA fragmentation, TUNEL assay, and caspase-3 activation. Results indicated the following: (i) the lipid fraction of oxLDL was primarily responsible for endothelial apoptosis. (ii) Endothelial apoptosis was potently inhibited by *NO donors and lipophilic phenolic antioxidants. OxLDL severely depleted Bcl-2 levels in endothelial cells and *NO donors restored Bcl-2 protein in oxLDL-treated cells. (iii) The pretreatment of a lipid fraction derived from oxLDL with sodium borohydride or potassium iodide completely abrogated apoptosis in endothelial cells, suggesting that lipid hydroperoxides induce apoptosis. (iv) Metalloporphyrins dramatically inhibited oxLDL-induced apoptosis in endothelial cells. Neither S-nitrosation of caspase-3 nor induction of Hsp70 appeared to play a significant role in the antiapoptotic mechanism of *NO in oxLDL-induced endothelial apoptosis. We propose that cellular lipid peroxyl radicals or lipid hydroperoxides induce an apoptotic signaling cascade in endothelial cells exposed to oxLDL, and that *NO inhibits apoptosis by scavenging cellular lipid peroxyl radicals.

Author List

Kotamraju S, Hogg N, Joseph J, Keefer LK, Kalyanaraman B

Authors

Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antioxidants
Aorta
Apoptosis
Caspase 3
Caspases
Catalase
Cattle
Cell Membrane Permeability
Cells, Cultured
DNA Fragmentation
Endothelium, Vascular
Enzyme Activation
Glutathione Peroxidase
HSP70 Heat-Shock Proteins
In Situ Nick-End Labeling
Iron Chelating Agents
Kinetics
Lipoproteins, LDL
Models, Biological
Nitrates
Nitric Oxide
Nitric Oxide Donors
Oxidants
Proto-Oncogene Proteins c-bcl-2
Superoxide Dismutase