Accumulation of altered aspartyl residues in erythrocyte membrane proteins from patients with sporadic amyotrophic lateral sclerosis
| Autor: | Luca Daniele, Maria Rosaria Monsurrò, Stefania D'Angelo, Marianna Raimo, Patrizia Galletti, Anna Salvatore, Francesca Trojsi |
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| Přispěvatelé: | D'Angelo, S, Trojsi, Francesca, Salvatore, A, Daniele, L, Raimo, M, Galletti, P, Monsurro', Maria Rosaria |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Cell type Oxidative phosphorylation medicine.disease_cause Cellular and Molecular Neuroscience Protein structure Methionine Protein D-Aspartate-L-Isoaspartate Methyltransferase medicine Humans Amyotrophic lateral sclerosis Deamidation Aged Aspartic Acid Chemistry Amyotrophic Lateral Sclerosis Erythrocyte Membrane Membrane Proteins Cell Biology Methionine Adenosyltransferase Middle Aged medicine.disease S-Adenosylhomocysteine In vitro Oxidative Stress Amyotrophic lateral sclerosis Erythrocytes Protein L-isoaspartyl/D-aspartyl Omethyltransferase S-Adenosylmethionine Protein deamidation Oxidative stress Biochemistry Female Reactive Oxygen Species Cell aging Oxidation-Reduction Oxidative stress |
| Popis: | Spontaneous protein deamidation of labile asparagines (Asn), generating abnormal l-isoaspartyl residues (IsoAsp), is associated with cell aging and enhanced by an oxidative microenvironment. The presence of isopeptide bonds impairs protein structure/function. To minimize the damage, IsoAsp can be "repaired" by the protein l-isoaspartyl/d-aspartyl O-methyltransferase (PIMT) and S-adenosylmethionine (AdoMet) is the methyl donor of this reaction. PIMT is a repair enzyme that initiates the conversion of l-isoAsp (or d-Asp) residues to l-Asp residues. Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease principally affecting motor neurons. The condition of oxidative stress reported in familial and sporadic forms of ALS prompted us to investigate Asn deamidation in ALS tissue. Erythrocytes (RBCs) were selected as a model system since they are unable to replace damaged proteins and protein methylesterification is virtually the only AdoMet-consuming reaction operating in these cells. Our data show that, in vitro assay, abnormal IsoAsp residues were significantly higher in ALS patients erythrocyte membrane proteins with an increased methyl accepting capability relative to controls (p |
| Databáze: | OpenAIRE |
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