5- and 6-glycosylation of transferrin in patients with Alzheimer's disease.
Transferrin is a glycosylated metal-carrying serum protein. One of the biological functions of glycosylation is to regulate the life span of proteins, less glycosylation leading to a faster clearance of a protein from the circulation. In the case of transferrin, this would indirectly also influence iron homeostasis. Higher glycosylation has been demonstrated in patients with Parkinson's disease and rheumatoid arthritis. A genetic variant of transferrin, TfC2, occurs with increased frequency in patients with Alzheimer's disease (AD), rheumatoid arthritis, and other diseases associated with a free radical etiology. Investigations have so far not revealed the reason for the pro-oxidative qualities of TfC2. In this study the glycosylation of Tf in AD (TfC1 homozygotes and TfC1C2 heterozygotes) was compared with alcohol-induced dementia (AID) patients and nondemented, age-matched controls, using isoelectric focusing followed by blotting with anti-Tf antibodies. In TfC1 homozygotes a shift was found toward higher sialylation, but in TfC1C2 heterozygotes the 5- and 6-sialylated bands were less concentrated. The decreased sialalytion found for TfC1C2 heterozygotes, may indicate that the pro-oxidative TfC2 molecules are removed from the circulation at a faster rate than TfC1. This may be of benefit to AD patients having TfC2, but still does not explain why this Tf variant is pro-oxidative.
van Rensburg
Susan J
SJ
Department of Chemical Pathology, National Health Laboratory Service, Tygerberg Hospital and Stellenbosch University, South Africa. sjvr@sun.ac.za
Berman
Peter
P
Potocnik
Felix
F
MacGregor
Pam
P
Hon
Dinie
D
de Villiers
Nico
N
D000437:Alcoholism / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006031:Glycosylation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007525:Isoelectric Focusing; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D010084:Oxidation-Reduction; D014168:Transferrin / Q000235:genetics* / Q000378:metabolism*
D005609:Free Radicals; D014168:Transferrin; D019158:N-Acetylneuraminic Acid