Peroxidative aggregation of myelin membrane proteins

Abstract

The exposure of CNS myelin to reactive oxygen species (ROS) generated by a Cu2+-H2O2 system results in the aggregation of membrane proteins. Integral and peripheral membrane proteins are equally vulnerable and the denaturation is not mediated by the SH groups. The aggregated proteins retain their original antigenicity as determined by immunoblot technique. The aggregation of proteins is not limited to myelin and can be elicited in the preparation of other cerebral membranes. The effect of ROS on membrane proteins can also be demonstrated in cerebral slices incubated in the presence of the ROS-generating system. Furthermore, the peroxidation inactivates membrane-bound enzymes as exemplified by myelin cyclic nucleotide phosphatase (CNP). Competitive inhibition studies with various scavengers and quenchers of ROS implicate singlet oxygen as a major mediator in the Cu2+-H2O2 oxidizing system responsible for the peroxidative aggregation of membrane proteins.