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. Design: 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. Discussion: 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.

Carelli-alinovi, C., Misiti, F., Methionine 35 sulphoxide reduces toxicity of Abeta in red blood cell, <<EUROPEAN JOURNAL OF CLINICAL INVESTIGATION>>, 2017; 47 (4): 314-321. [doi:10.1111/eci.12735] [http://hdl.handle.net/10807/113474]

Methionine 35 sulphoxide reduces toxicity of Abeta in red blood cell

Carelli-Alinovi, Cristiana
Primo
;
Misiti, Francesco
Ultimo
2017

Abstract

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. Design: 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. Discussion: 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.
Inglese
Carelli-alinovi, C., Misiti, F., Methionine 35 sulphoxide reduces toxicity of Abeta in red blood cell, <<EUROPEAN JOURNAL OF CLINICAL INVESTIGATION>>, 2017; 47 (4): 314-321. [doi:10.1111/eci.12735] [http://hdl.handle.net/10807/113474]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/113474
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