Methionine 35 oxidation reduces toxic effects of the amyloid β-protein fragment (31–35) on human red blood cell

• Published in: The international journal of biochemistry & cell biology Vol. 36; no. 10; pp. 2066 - 2076
• Main Authors: Clementi, Maria Elisabetta, Martorana, Giuseppe Ettore, Pezzotti, Michela, Giardina, Bruno, Misiti, Francesco
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.2004
• Subjects: Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - toxicity; Aβ peptide; Catalase; Catalase - metabolism; Erythrocyte; Erythrocytes - drug effects; Erythrocytes - metabolism; Erythrocytes - pathology; Glucosephosphate Dehydrogenase - metabolism; Glutathione Peroxidase - metabolism; Glutathione Reductase - metabolism; Hemoglobin; Hemoglobins - metabolism; Humans; Kinetics; Methionine; Methionine - metabolism; Oxidation-Reduction; Pentose phosphate pathway; Peptide Fragments - metabolism; Peptide Fragments - toxicity; Phosphofructokinases - metabolism; Erythrocyte; PPP; G6PD; Aβ peptide; PFK; Catalase; CAT; Methionine; Pentose phosphate pathway; Hemoglobin; GR; GPx
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2004.03.006

Amyloid β-peptide, the central constituent of senile plaques in Alzheimer’s disease brain, has been shown to be a source of free radical oxidative stress that may lead to neurodegeneration. In particular, it is well known that oxidation of methionine 35, is strongly related to the pathogenesis of Alzheimer’s disease, since it represents the residue in the β-amyloid peptide most susceptible to oxidation “in vivo”. In this study, the fragment 31–35 of the β-amyloid peptide, which has a single methionine at residue 35, was used to investigate the influence of the oxidation state of methionine-35 on the β-amyloid peptide (31–35) mediated cytotoxic effects. Because no extensive studies have yet addressed whether amyloid β peptides-mediated toxic effects can occur in the absence of mitochondria, human red blood cells were used as cell model. Exposure of intact red blood cells to β-amyloid peptide (31–35) induced a marked stimulation (∼45%) of the pentose phosphate pathway and a significant inhibition of the red cell enzyme catalase, compared with the results observed in control red blood cells. In contrast, exposure of red blood cells to the β-amyloid peptide (31–35)-Met35 OX i.e. in which the sulfur of methionine is oxidised to sulfoxide, induced a slight activation of PPP (∼19%), and an inhibition of catalase activity lower with respect to the results observed in β-amyloid peptide (31–35)-treated red blood cells. Since the activities of red cell phosphofructokinase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase and the functionality of hemoglobin were not modified within the red cell following to β-amyloid peptides exposure, it is likely that β-amyloid (31–35)–catalase interaction may represent a selective toxic event. Together, these results support the hypothesis that Aβ peptide and the oxidative state of Met-35 may be involved in the mechanisms responsible of neurodegeneration in Alzheimer’s disease.