Methionine 35 sulphoxide reduces toxicity of Aβ in red blood cell.
BACKGROUND
The oxidation of methionine residue in position 35 of Ab to sulphoxide (Ab-sulphoxide) has the ability to deeply modify wild-type Ab 1-42 (Ab) neurotoxic action. Our previous studies suggest that in nucleated cells, lower toxicity of Ab-sulphoxide might result not from structural alteration, but from elevation of methionine sulphoxide reductase A (MsrA) activity and mRNA levels.


METHODS
On this basis, we hypothesised that red blood cell (RBC), a cell devoid almost completely of MsrA activity, shares with nucleated cells an antioxidant system induced by methionine 35 sulphoxide, responsible for the lower toxicity of Ab-sulphoxide in RBC. (Results) Supporting this hypothesis, we found that the low toxicity of Ab-sulphoxide in RBC correlated with pentose phosphate pathway (PPP) flux increase, and this event was associated with a low level of methionine oxidation in total proteins. None of these effects were observed when cells were exposed to Ab native.


CONCLUSIONS
These results outline the importance of the redox state of methionine 35 in the modulation of Ab-mediated events and suggest an important protective role for PPP in RBC of patients affected by Alzheimer's disease.
School of Medicine, Biochemistry and Clinical Biochemistry Institute, Catholic University, Rome, Italy.
Cristiana
C
Carelli-Alinovi
Human Sciences, Society and Health Department, University of Cassino and Southern Lazio, Cassino, Italy.
Francesco
F
Misiti
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D064368:Healthy Volunteers; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives* / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000502:physiology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D008715:Methionine; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D053148:Caspase 3; D005947:Glucose; C013111:methionine sulfoxide
Alzheimer's disease; amyloid beta-peptide (1-42); caspase 3; methionine 35; oxidative stress; pentose phosphate pathway; red blood cell