Batzlsperger, Christian A. and Achatz, Stefan and Spreng, Josefine and Riegger, Guenter A. J. and Griese, Daniel P. (2007) Evidence for a possible inhibitory interaction between the HO-1/CO- and Akt/NO-Pathways in human endothelial cells. CARDIOVASCULAR DRUGS AND THERAPY, 21 (5). pp. 347-355. ISSN 0920-3206,
Full text not available from this repository. (Request a copy)Abstract
Objective The protective properties of heme oxygenase 1 (HO-1) give reason to study this mechanism as a potential therapeutic target for inflammatory and cardiovascular diseases. Recent evidence suggests a possible interaction between the HO-1/CO- and the protein kinase Akt/NO-pathway. This study was designed to examine the effects of continuous HO-1 overexpression in endothelial cells. Methods Oncoretroviral vectors were constructed to achieve constitutive overexpression of HO-1, Akt, and green fluorescence protein in human umbilical vein endothelial cells. [H-3]thymidine-incorporation and lipid-peroxidation were measured following exposure to heme and H2O2. Expression of HO-1, Akt and its downstream-target endothelial NO-synthase were quantified by Western blot analysis. NO-synthase-activity was measured using the citrulline-conversion-assay. Results HO-1-overexpression reduced proliferative rates and DNA-synthesis of HUVEC, but provided potent protection from oxidative stress induced by heme and H2O2. Phosphorylated-Akt and eNOS was downregulated in HO-1-HUVEC. eNOS-activity was reduced in HO-1-HUVEC. Co-infection with the Akt-retrovirus restored proliferative rates and eNOS-expression and -activity. Conclusion Continuously elevated HO-1-activity protects EC from oxidative stress but inhibits Akt-mediated proliferation and eNOS-expression. This inhibitory feedback mechanism could be a limitation of HO-1 as a target for the treatment of vascular disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEME OXYGENASE-1 EXPRESSION; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE AKT; CARBON-MONOXIDE; GENE DELIVERY; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; INJURY; TRANSPLANTATION; PROTECTION; endothelial function; heme oxygenase 1; protein kinase Akt; oxidative stress; nitric oxide |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Dec 2020 08:57 |
| Last Modified: | 01 Dec 2020 08:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32099 |
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