Increased susceptibility to degradation by trypsin and subtilisin of in vitro peroxidized myelin proteins.
We examined the possibility that the peroxidative damage to central nervous system myelin produced by reactive oxygen species (ROS), could modify the susceptibility of its proteins to the proteolytic action of proteases such as trypsin and subtilisin. Purified myelin membranes obtained from adult rat brains were "in vitro" peroxidized by two non-enzymatic systems: Fe3+ plus ascorbic acid and Cu2+ plus hydrogen peroxide. Myelin proteins were severely affected by peroxidation. There was an increase in the amount of carbonyl groups (CO), accompanied by an enhanced susceptibility to degradation by trypsin and subtilisin of myelin basic proteins (MBP) and of the major proteolipid protein (PLP). The effect upon the degradation of myelin protein is a possible consequence of the appearance in the structure of myelin proteins of peroxidative modifications that contribute to the recognition by proteolytic enzymes. This hypothesis is supported by the fact that if peroxidation of myelin membranes is done in the presence of EDTA, both CO formation and increased sensitivity to enzymatic breakdown disappear. These results suggest that the appearance of abnormal post-translational modifications in the myelin membrane produced by peroxidation could constitute a putative mechanism of modulating the capacity of myelin proteins to be metabolized by proteases.
Bongarzone
E R
ER
Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Soto
E F
EF
Pasquini
J M
JM
D000818:Animals; D002384:Catalysis; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009185:Myelin Proteins / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013381:Subtilisins / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism*
D009185:Myelin Proteins; D017382:Reactive Oxygen Species; D010544:Peroxidases; D013381:Subtilisins; D014357:Trypsin