Rostov-on-Don, Rostov-on-Don, Russian Federation
Rostov-on-Don, Rostov-on-Don, Russian Federation
Rostov-on-Don, Rostov-on-Don, Russian Federation
Rostov-on-Don, Rostov-on-Don, Russian Federation
Rostov-on-Don, Rostov-on-Don, Russian Federation
The administration of SkQ1 (50 nmol/kg for 5 days) significantly increased mRNA level of transcription factor Nrf2 and Nrf2-controlled genes encoding antioxidant enzymes SOD1 , SOD2 , and CAT with inconsiderable changes in mRNA level of SOD3 and GPx4 in the cerebral cortex of rat brain. This was accompanied by the activation of antioxidant enzymes (SOD, CAT, GPx, GST) and increase in reduced glutathione level. Hyperoxia-induced oxidative stress (0.5 Pa for 90 min) decreased the mRNA level of transcription factor Nrf2; the changes in transcriptional activity of Nrf2-induced genes encoding antioxidant enzymes ( SOD1-3 , CAT , GPx4 ) were insignificant in rat cerebral cortex. Hyperoxia resulted in increased lipid peroxidation intensity, inhibition of CAT, and increase in GST activity, and maintenance of stationery level of SOD and GPx activity in rat cerebral cortex. Pretreatment with SkQ1 before hyperoxic exposure lead to increase in mRNA level of transcription factor Nrf2 and Nrf2-induced genes encoding antioxidant enzymes SOD1-2 , CAT , and GPx4 ; SOD3 expression was unchanged in the cerebral cortex under oxidative stress. The activity of these antioxidant enzymes (SOD, CAT, GPx, GST) and reduced glutathione level were concurrently increased. The effect of the mitochondria-targeted antioxidant SkQ1 on the level of expression of the CASP3 gene and the caspase-3 activity in the cortex of the cerebral hemispheres was studied in normal conditions and in HBO-induced oxidative stress. It was found that under physiological conditions the applying of SkQ1 (50 nmol/kg, 5 days) does not lead to a change in the expression of the CASP3 gene and caspase-3 activity in the cells of the cerebral cortex. In HBO-induced oxidative stress (0.5 MPa, 90 min), a significant increase in the mRNA level of the CASP3 gene and caspase-3 activity in the cortex of the cerebral hemispheres was revealed. The preliminary applying of SkQ1 before the HBO session promotes maintaining the basal level of expression of the CASP3 gene and the activity of the enzyme in the cells of the cerebral cortex and also leads to the normalization of caspase-3 activity. We suggest that the protective effect of SkQ1 under hyperoxia-induced oxidative stress may be realized via direct antioxidant activity, the activation of defense system Keap1/Nrf2/ARE and stimulation of antiapoptotic mechanisms.
-3, oxidative stress, hyperoxia, mitochondria-targeted antioxidant, brain, gene expression, antioxidant enzymes, caspase-3
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