TY - JOUR
T1 - Protein nitration profile of CD3+ lymphocytes from Alzheimer disease patients
T2 - Novel hints on immunosenescence and biomarker detection
AU - Tramutola, Antonella
AU - Abate, Giulia
AU - Lanzillotta, Chiara
AU - Triani, Francesca
AU - Barone, Eugenio
AU - Iavarone, Federica
AU - Vincenzoni, Federica
AU - Castagnola, Massimo
AU - Marziano, Mariagrazia
AU - Memo, Maurizio
AU - Garrafa, Emirena
AU - Butterfield, D. Allan
AU - Perluigi, Marzia
AU - Di Domenico, Fabio
AU - Uberti, Daniela
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/12
Y1 - 2018/12
N2 - Alzheimer's disease (AD) is a progressive form of dementia characterized by increased production of amyloid-β plaques and hyperphosphorylated tau protein, mitochondrial dysfunction, elevated oxidative stress, reduced protein clearance, among other. Several studies showed systemic modifications of immune and inflammatory systems due, in part, to decreased levels of CD3+ lymphocytes in peripheral blood in AD. Considering that oxidative stress, both in the brain and in the periphery, can influence the activation and differentiation of T-cells, we investigated the 3-nitrotyrosine (3-NT) proteome of blood T-cells derived from AD patients compared to non-demented (ND) subjects by using a proteomic approach. 3-NT is a formal protein oxidation and index of nitrosative stress. We identified ten proteins showing increasing levels of 3-NT in CD3+ T-cells from AD patients compared with ND subjects. These proteins are involved in energy metabolism, cytoskeletal structure, intracellular signaling, protein folding and turnover, and antioxidant response and provide new insights into the molecular mechanism that impact reduced T-cell differentiation in AD. Our results highlight the role of peripheral oxidative stress in T-cells related to immune-senescence during AD pathology focusing on the specific targets of protein nitration that conceivably can be suitable to further therapies. Further, our data demonstrate common targets of protein nitration between the brain and the periphery, supporting their significance as disease biomarkers.
AB - Alzheimer's disease (AD) is a progressive form of dementia characterized by increased production of amyloid-β plaques and hyperphosphorylated tau protein, mitochondrial dysfunction, elevated oxidative stress, reduced protein clearance, among other. Several studies showed systemic modifications of immune and inflammatory systems due, in part, to decreased levels of CD3+ lymphocytes in peripheral blood in AD. Considering that oxidative stress, both in the brain and in the periphery, can influence the activation and differentiation of T-cells, we investigated the 3-nitrotyrosine (3-NT) proteome of blood T-cells derived from AD patients compared to non-demented (ND) subjects by using a proteomic approach. 3-NT is a formal protein oxidation and index of nitrosative stress. We identified ten proteins showing increasing levels of 3-NT in CD3+ T-cells from AD patients compared with ND subjects. These proteins are involved in energy metabolism, cytoskeletal structure, intracellular signaling, protein folding and turnover, and antioxidant response and provide new insights into the molecular mechanism that impact reduced T-cell differentiation in AD. Our results highlight the role of peripheral oxidative stress in T-cells related to immune-senescence during AD pathology focusing on the specific targets of protein nitration that conceivably can be suitable to further therapies. Further, our data demonstrate common targets of protein nitration between the brain and the periphery, supporting their significance as disease biomarkers.
KW - Alzheimer's disease
KW - CD3 lymphocytes
KW - Immunesenescence
KW - Oxidative stress
KW - Protein nitration
KW - Proteomics
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U2 - 10.1016/j.freeradbiomed.2018.10.414
DO - 10.1016/j.freeradbiomed.2018.10.414
M3 - Article
C2 - 30321702
AN - SCOPUS:85055168925
SN - 0891-5849
VL - 129
SP - 430
EP - 439
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -