Sid Ahmed-Adrar, N., Collin, F., Couturier, M., Vitrac, H., Bonnefont-Rousselot, D., Jore, D. and Gardès-Albert, M. Radiolytic Yield of Cardiolipin Peroxidation by Gamma Rays in Large Unilamellar Vesicles of Phosphatidylcholine. Radiat. Res. 171, 622–630 (2009).

Large unilamellar vesicles of 1-hexanoyl-2-(9Z-12Z-octadecadienoyl)-sn-glycero-3-phosphocholine (PLPC) have been used as model membrane to investigate the effect of increasing amount of cardiolipin (1′,3′-bis-[1,2-Di-(9Z-12Z-octadecadienoyl)-sn-glycero-3-phospho]-sn-glycerol, CL) on the peroxidizability of the lipid phase. Hydroxyl radicals generated by gamma radiolysis of water initiated the lipid peroxidation. Both peroxidation products (conjugated dienes and hydroperoxides of PLPC, mono- and dihydroperoxides of CL) and disappearance of CL and PLPC were assessed as a function of the radiation dose (25 to 400 Gy, I = 10 Gy min⁻¹). Our results show that the addition of 5% to 15% CL to large unilamellar vesicles (concentration ratio) produces almost complete inhibition of PLPC peroxidation. Thus, for 15% CL (known to be the proportion of CL in the inner mitochondrial membrane), the radiolytic yield of formation of PLPC hydroperoxides is reduced to zero, whereas it is equal to (3.1 ± 0.2) × 10⁻⁷ mol J⁻¹ for CL hydroperoxides, showing the importance of the targeted CL. For this concentration ratio (CL/ PLPC 15%), we have established the balance equation between the consumption of CL [G(–CL) = (2.8 ± 0.1) × 10⁻⁷ mol J⁻¹] and the formation of CL hydroperoxides [G(CLOOH_T) = (3.1 ± 0.2) × 10⁻⁷ mol J⁻¹]. In addition, the radiolytic yields of disappearance of PLPC and CL have been determined [(1.5 ± 0.1) × 10⁻⁷ mol J⁻¹ and (2.8 ± 0.1) × 10⁻⁷ mol J⁻¹, respectively], their sum [(4.3 ± 0.2) × 10⁻⁷ mol J⁻¹] being higher than G_HO· (2.8 × 10⁻⁷ mol J⁻¹). However, there is no balance between the radiolytic yield of formation of PLPC hydroperoxides [G (PCOOH_T) ∼ 0] and the yield of disappearance of PLPC [(1.5 ± 0.1) × 10⁻⁷ mol J⁻¹], likely because lipid fragments (not measured in this work) could be generated from HO^· reaction on the polar head of PLPC. These results have been interpreted by assuming that the hydroxyl radicals attack in competition both lipid targets, i.e. PLPC and CL, with a higher sensitivity to CL oxidation. It can be concluded that a little amount of CL (10–15% CL/ PLPC concentration ratio) may exert a strong protective effect against the HO^·-induced peroxidation of PLPC.