Expression changes of human mitochondrial COX genes in human lymphocytes after exposed by ⁶⁰Co γ-rays

Objective: To explore the changes of human mitochondrial COX Ⅰ , COX Ⅱ and COX Ⅲ genes expression induced by ionizing irradiation. Methods: Changes of human COX genes expression were detected by RT-PCR and Real-time PCR 8 h after the irradiation in human lymphoblastoid cell lines,which were exposed to 1-10 Gy ⁶⁰Co γ-rays. The protein levels were detected by flow cytometry and the COX activity was measured by colorimetry. The dose-effect relationships between the expression changes of the genes and the doses were established. The changes of these genes expression were also analyzed at different post-radiation time-points between 0.5 h and 72 h after irradiation of 5 Gy in order to explore the time-effect. Results: The expression of 3 genes at mRNA level was up-regulated. A good dose-effect relationship was showed for COXⅠ and COX Ⅲ at dose range of 0-3 Gy and 0-8 Gy for COX Ⅱ (F_COXⅠ=116. 62, F_COXⅡ=17. 89, F_COXⅢ = 8.20, P<0.05). For the time-effect after irradiation, the gene expression levels of COX Ⅱ and COX Ⅲ genes were up-regulated and the peak change occurred at 4 h after irradiation. For COX Ⅰ gene, the mRNA expression levels were down-regulated during 0.5-72 h (F_COXⅠ=31.99, F_COXⅡ=19.47, F_COXⅢ=20.64, P<0.05 ). At the protein level, the levels of COX Ⅰ and COX Ⅱ were lowered in lower doses and enhanced in higher doses, and the levels of COX Ⅲ were decreased at all dose levels (F_COXⅠ=16.96, F_COXⅡ=32.5, F_COXⅢ=6.51, P<0.05). The protein levels of COX Ⅰ and COX Ⅱ were enhanced during 4-72 h and 8-72 h respectively after 5 Gy irradiation (F_COXⅠ=14.68,F_COXⅡ=17.18, F_COXⅢ =2.52, P<0.05). The activities of COX were lowered at different dose levels and different time-points. Conclusions: Ionizing radiation might induce the changes in mitochondrial COX Ⅰ, COX Ⅱ and COX Ⅲ gene expression, and lead to the reduction of the COX activities. (authors)