Abstract
Aspirin is known to exert antioxidant effects by as yet unidentified mechanisms. In cultured endothelial cells derived from human umbilical vein, aspirin (30-300μM) increased heme oxygenase-1 (HO-1) protein levels in a concentration-dependent fashion up to fivefold over basal levels. HO-1 induction was accompanied by a marked increase in catalytic activity of the enzyme as reflected by enhanced formation of both carbon monoxide and bilirubin. Pretreatment with aspirin or bilirubin at low micromolar concentrations protected endothelial cells from hydrogen peroxide-mediated toxicity. HO-1 induction and endothelial protection by aspirin were not mimicked by indomethacin, another inhibitor of cyclooxygenase. The nitric oxide (NO) synthase blocker L-NAME prevented aspirin-dependent HO-1 induction. These findings demonstrate that aspirin targets HO-1, presumably via NO-dependent pathways. Induction of HO-1 expression and activity may be a novel mechanism by which aspirin prevents cellular injury under inflammatory conditions and in cardiovascular disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 956-960 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 308 |
| Issue number | 4 |
| DOIs | |
| State | Published - Sep 5 2003 |
Keywords
- Antioxidant
- Aspirin
- Bilirubin
- Carbon monoxide
- Cell injury
- Cytoprotection
- Endothelial cells
- Gene expression
- Heme oxygenase
- Nitric oxide
