ИСТИНА

Interaction of cytochrome c with mitochondrial cardiolipin is known to convert this electron transfer protein into peroxidase, which is supposed to play an essential role in apoptosis. Cytochrome c/cardiolipin peroxidase activity has been found previously to cause permeabilization of liposome membranes, in particular, leakage of fluorescent probes, such as carboxyfluorescein, calcein, sulforhodamine B and 3-kDa (but not 10-kDa) fluorescent dextran from liposomes. Studies of the effect of the combination of cytochrome c with hydrogen peroxide on the conductance of planar bilayer lipid membranes (BLM) have shown the ability of this electron-transfer protein to form ion channels under the oxidative stress conditions. Here, we examined the impact of membrane lipid composition on the activity of ion channels formed by cytochrome c in planar BLM in the presence of hydrogen peroxide. According to our results, the addition of cytochrome c with hydrogen peroxide to the bathing solution at both sides of the BLM led to the appearance of regular fluctuations of the electric current across BLM with the amplitude of about 0.8 nS under the conditions of low ionic strength. The presence of about 20% cardiolipin in the BLM composition was mandatory for the formation of these ion channels. The conductance of the cytochrome c ion channels was higher with equine heart cardiolipin, than with synthetic tetraoleoyl cardiolipin. Apart from the presence of cardiolipin, the activity of the cytochrome c ion channels was sensitive to the composition of the bulk membrane-forming lipid. In particular, no ion channels were observed, if soybean phosphatidylcholine (asolectin), comprising 80% of the membrane lipid in the above experiments, was replaced by dilinoleoyl phosphatidylcholine or dierucoyl phosphatidylcholine. The induction of ion channels by cytochrome c with hydrogen peroxide in planar BLM was suppressed by antioxidants, such as Trolox.