Oxidative modification of collagen by malondialdehyde in porcine skin

Human skin is exposed to various physical and chemical stress factors, which commonly cause the oxidation of lipids and proteins. In this study, azo initiator AAPH [2,2 ' -azobis(2-methylpropionamidine) dihydrochloride] was employed to initiate lipid peroxidation in porcine skin as an ex vivo model for human skin. We demonstrate that malondialdehyde (MDA), a secondary product of lipid peroxidation, is covalently bound to collagen in the dermis, forming MDA-collagen adducts. The binding of MDA to collagen results in an unfolding of the collagen triple helix, formation of the dimer of alpha-chains of collagen, and fragmentation of the collagen alpha-chain. It is proposed here that the MDA is bound to the lysine residues of alpha-chain collagen, which are involved in electrostatic interaction and hydrogen bonding with the glutamate and aspartate of other alpha-chains of the triple helix. Our data provide crucial information about the MDA binding topology in the skin, which is necessary to understand better the various types of skin-related diseases and the aging process in the skin under stress.