MiP2005: Session 2

Mitochondrial Physiology Network 10.9: 29-30 (2005) - download pdf


Different regimen of intermittent hypoxia training (IHT) as modulators of heart mitochondrial membrane permeability transition.

Tatiana V Serebrovskaya, GL Vavilova, OV Rudyk, MV Belikova, EE Kolesnikova, TV Kukoba, VF Sagach

Bogomoletz Institute of Physiology, Kiev 01024, Ukraine. - sereb@mail.kar.net

    IHT is believed to induce myocardial protection. We hypothesized that inhibiting of mitochondrial permeability transition pore (mPTP) opening by means of antioxidant system promotion is one of the key elements of such protection, and mitochondrial swelling rate depends on degree of hypoxic exposure. Four groups of male adult Wistar rats participated in the study. Animals of Gr. 1 underwent daily sham IHT (control group). Gr. 2–4 were exposed for 2 weeks to IHT in two regimen: R1- breathing in normobaric chamber with 11 % O2 gas mixture, 15-min sessions with 15 min rest intervals, 5 times daily (Gr. 2); R2 – breathing with 8 % O2,  5-min sessions with 15 min rest intervals, 5 times daily (Gr. 3-4). Gr. 1-3 were examined next day after IHT, Gr. 4 – in 45 days after IHT stopping. Phenylarsineoxide (PAO)-induced mitochondrial swelling rate was investigated spectrophotometrically (λ = 520 nm) in isolated heart mitochondria by a decrease in their optical density after 20 min of incubation with PAO. The intensity of lipid peroxidation and antioxidant defense mechanisms in rat organism were estimated before and after IHT by measuring of malon dialdehyde (MDA) content and the activity of superoxide dismutase (SOD) and catalase (CAT) in blood and liver. It was shown that the training with moderate hypoxia (R1) did not essentially influence mPTP opening nor free radical production: The magnitude of mitochondrial swelling in Gr. 2 under incubation with PAO in concentrations 10-5 and 10-4 mol/l was almost the same as in Gr. 1; MDA content decreased by 10 and 20 % in blood and liver, respectively; a slight increase in superoxide dismutase activity by 29 и 23%, a decrease in catalase activity by 9 % (ns) and 21 %, respectively, was observed. The training with more severe hypoxia (R2) provoked a two-fold decrease in PAO-induced mitochondrial swelling (Gr. 3 compared with Gr. 1). And even in 45 days (Gr. 4) the protective effects of R2  on mitochondria were well-preserved. These effects were completely abolished in the presence of cyclosporin A (10-5 mol/l), indicating that mitochondrial swelling was due to mitochondrial permeability transition pore opening. Simultaneously, R2 training caused pronounced increases in MDA content both in blood and liver by 67 and 32 %, respectively, and considerable augmentation in activities of SOD (49 and 32 %) and CAT (18 and 43 %). Moreover, in 45 days the activity of SOD exceeded initial levels three-fold both in blood and liver. Taken together, moderate intermittent hypoxia which provokes some inhibition of lipid peroxidation with slight increase in antioxidant activity, does not influence PAO-induced mitochondrial swelling. A more severe regime of IHT, stimulating both the increase of lipid peroxidation and strongly pronounced augmentation of antioxidant system, causes a stable increase in resistance of mitochondrial membrane to PAO. Probably, intensified free radical production during more severe hypoxia could serve as a trigger in signal transduction cascades and lead to increase in antioxidant defence and thus to mitochondria protection. IHT can be used as protective procedure preventing mitochondria from damage.

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Mitochondrial Physiology