Project Details
Description
Heme oxygenase-1 (HO), a stress-inducible protein, is an important cytoprotective agent against various oxidative stresses. Traditionally, the protective properties of HO-1 have been attributed to the by-products of heme degradation, namely bilirubin and CO. Emerging evidences indicated that HO-1 may also exert cytoprotective effects, independent of heme breakdown, by interacting with survival signaling pathways such as PI3K/Akt and p38 pathway. At least in myocardium and endothelial cells, biliverdin reductase (BVR), the downstream enzyme of heme degradation was found to be important to the cytoprotection of HO-1. It was reported that BVR may function as a serine/ threonine kinase to phosporylate the PI3K p85, and activate PI3K/Akt survival pathway. The skin is continuously exposed to environmental insults including UV radiation and high oxygen concentration, which constantly jeopardize the integrity of the skin. The reactive oxygen species (ROS) formed under these conditions is presumed to play an important role in carcinogenesis, skin aging and skin diseases. HO-1 mRNA can be induced by ROS and UVA irradiation in the epidermis, which was considered to be cytoprotective. However, the underlying mechanism of HO-1 protection from epidermal apoptosis was not clear. Our specific aim is to investigate the mechanism by which the HO-1 protects epidermis from H2O2- and UVB irradiation- induced epidermal apoptosis. Two kinds of flavonoids- baicalein (BE) and quercetin (QE) are used as topical HO-1 inducer to evaluate the inhibition of apoptosis by HO-1 in vivo. Our hypothesis is the inhibitory effect of HO-1 on UVB- induced epidermal apoptosis is dependent on BVR (biliverdin reductase) and its interaction with PI3K-Akt pathway.
Status | Finished |
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Effective start/end date | 8/1/10 → 7/31/11 |
Keywords
- Heme oxygenase-1 (HO-1)
- Biliverdin reductase (BVR)
- PI3K/Akt
- baicalein
- quercetin
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