Kidney-to-brain cross-talk as a way to ameliorate brain damage after brain ischemiaтезисы доклада

Дата последнего поиска статьи во внешних источниках: 28 мая 2015 г.

Работа с тезисами доклада


[1] Kidney-to-brain cross-talk as a way to ameliorate brain damage after brain ischemia / D. Silachev, N. Isaev, I. Pevzner et al. // Febs Journal Special Issue: 38th FEBS Congress, Saint Petersburg, Russia, July 6–11, 2013. — Vol. 280 of Special Issue: 38th FEBS Congress, Saint Petersburg, Russia, July 6–11, 2013. — 2013. — P. 425–425. Since certain brain pathologies can be attributed to the consequences of oxidative stress, antioxidant treatment may be an effective approach. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than other cellular compartments. We showed the neuroprotective effect of mitochondria-targeted antioxidant SkQR1 in a few models of brain ischemia. Also we demonstrate that SkQR1 is able to induce some elements of ischemic tolerance pathways such as an increase in erythropoietin (EPO) levels and phosphorylation of glycogen synthase kinase 3b (GSK-3b) in the kidney. The regulation of EPO production is believed to involve activation of the hypoxia-inducible transcription factor (HIF-1a), which depends on redox-sensitive stabilization of its a subunit. Redox-dependence of EPO expression allows speculating on existence of the mechanism of indirect neuroprotective action of antioxidants mediated by the kidney which is the main EPO-producing organ. To test this hypothesis we used ischemic preconditioning of the kidney that is believed to cause enhanced EPO release. The goal of our study was to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. We used a mitochondria-targeted antioxidant, SkQR1, as a potential agent to alleviate the deleterious consequences of stroke. Single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduced brain damage and improved functional recovery. Concomitantly, an increase in the levels of EPO in urine and phosphorylated GSK-3b in the brain was detected 24 hours after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s) which are released from functional kidneys. Renal preconditioning also induced brain protection accompanied by an increased EPO level in urine and kidney tissue and P-GSK-3b in brain. Co-cultivation of SkQR1-treated kidney cells with cortical neurons resulted in enhanced phosphorylation of GSK-3b in neuronal cells. The results indicate that preconditioning-induced and SkQR1- induced brain protection may be mediated through the release of EPO from the kidney.

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