Article

Amelioration of radiation-induced skin injury by adenovirus-mediated heme oxygenase-1 (HO-1) overexpression in rats.

School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.
Radiation Oncology (impact factor: 2.32). 01/2012; 7:4. DOI:10.1186/1748-717X-7-4
Source: PubMed

ABSTRACT Radiation-induced skin injury remains a serious concern for radiation therapy. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, has been reported to have potential antioxidant and anti-apoptotic properties. However, the role of HO-1 in radiation-induced skin damage remains unclear. This study aims to elucidate the effects of HO-1 on radiation-induced skin injury in rats.
A control adenovirus (Ad-EGFP) and a recombinant adenovirus (Ad-HO1-EGFP) were constructed. Rats were irradiated to the buttock skin with a single dose of 45 Gy followed by a subcutaneous injection of PBS, 5 × 109 genomic copies of Ad-EGFP or Ad-HO1-EGFP (n = 8). After treatment, the skin MDA concentration, SOD activity and apoptosis were measured. The expression of antioxidant and pro-apoptotic genes was determined by RT-PCR and real-time PCR. Skin reactions were measured at regular intervals using the semi-quantitative skin injury score.
Subcutaneous injection of Ad-HO1-EGFP infected both epidermal and dermal cells and could spread to the surrounding regions. Radiation exposure upregulated the transcription of the antioxidant enzyme genes, including SOD-1, GPx2 and endogenous HO-1. HO-1 overexpression decreased lipid peroxidation and inhibited the induction of ROS scavenging proteins. Moreover, HO-1 exerted an anti-apoptotic effect by suppressing FAS and FASL expression. Subcutaneous injection of Ad-HO1-EGFP demonstrated significant improvement in radiation-induced skin injury.
The present study provides evidences for the protective role of HO-1 in alleviating radiation-induced skin damage in rats, which is helpful for the development of therapy for radiation-induced skin injury.

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Keywords

anti-apoptotic effect
 
anti-apoptotic properties
 
antioxidant enzyme genes
 
buttock skin
 
endogenous HO-1
 
FASL expression
 
HO-1 overexpression
 
lipid peroxidation
 
pro-apoptotic genes
 
protective role
 
radiation-induced skin damage
 
Radiation-induced skin injury
 
rate-limiting enzyme
 
real-time PCR
 
regular intervals
 
semi-quantitative skin injury score
 
single dose
 
skin MDA concentration
 
subcutaneous injection
 
suppressing FAS