Induction of Heme Oxygenase By a Carbon Monoxide-Releasing Molecule

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.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Physiology

Year dc:date.available

2007

Author dc:creator

• Kulina, Robert Andrew

Contributors dc:contributor

• Dr. Dorne Yager

• heme oxygenase
• carbon monoxide
• CORM
• heme
• Life Sciences
• Physiology

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/1024

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-2023