We have recently demonstrated that heme oxygenase is expressed in both healing wounds and in pressure ulcers. Heme oxygenase has been shown to have important cytoprotective functions in myocardial ischemia-reperfusion injury and organ allograft survival. The cytoprotective effects of heme oxygenase are multifactorial. Besides reducing levels of pro-oxidant heme, heme oxygenase products (bilirubin, carbon monoxide, and iron) have been demonstrated to possess anti-oxidant, anti-inflammatory, anti-apoptotic, and anti-proliferative properties. These properties make heme oxygenase an attractive therapeutic target for the prevention and treatment of chronic wounds. The purpose of this study was two-fold: evaluate the effects of carbon monoxide (CO) on the expression of heme oxygenase (HO-1) in dermal fibroblasts, and determine and begin to investigate the mechanisms responsible for CO-induction of HO-1. The ability of a second-generation carbon monoxide donating molecule-tricarbonyldichlororuthenium (II) dimer (CORM-2) to induce HO-1 protein expression in dermal fibroblasts was examined. Western blotting techniques were utilized to determine HO-1 expression. CORM-2 (100-300uM) induced maximum expression of HO-1. The maximum response to CORM-2 occurred between 12 and 20 hours. Inhibition of MAPK, PI3-K, JNK pathways showed no changes in HO-1 expression. Likewise inhibition of cGMP, a known pathway for CO, had no effect on protein expression suggesting that HO-1 expression by CORM-2 works by an alternate pathway. In conclusion the ability of CO, a product of heme degradation, to induce HO-1 in dermal fibroblasts may serve as a mechanism to amplify HO-1 expression in stressed tissues and may serve as the basis for a novel therapeutic approach for treating chronic wounds.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-2023 |
| Date | 01 January 2007 |
| Creators | Kulina, Robert Andrew |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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