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P3‐337: Potential of zinc as an antiapoptotic agent during aluminium‐induced neurodegeneration
Author(s) -
Dhawan Devinder,
Singla Neha
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1561
Subject(s) - apoptosis , neurodegeneration , chemistry , zinc , caspase 3 , neurotoxicity , acridine orange , medicine , endocrinology , pharmacology , biochemistry , toxicity , biology , programmed cell death , disease , organic chemistry
kg/day) or control diet for 16 weeks. Thereafter, mice were transcardially perfused and pial-arteries surgically removed. Arterial proteins were extracted, trypsin-digested, fractionated by strong cation exchange (gel-free-method) and 1D SDS-PAGE (gel-based-method), and analyzed by nanoLC-MS/MS using nanoAcquity UPLC (Waters) and ESI-LTQ Orbitrap (Thermo). Protein identification was performed using Mascot. MatchRx software was used for alignment and quantification across the multiple samples, and peptide intensity validation was performed using MSight. Differentially-expressed proteins were identified at 1.5 and 2 fold-changes, and at p 0.05 and p 0.01. Three biological and two technical replicates were conducted. Results: We identified 6,566 pial-arterial proteins, of which 975 (15%) were differentially-expressed between WT and APP mice at fold-change 1.5 and p 0.05. The altered proteins were associated with biological pathways related to amyloidosis, oxidative stress and vasomotricity, as well as processes over-represented in the AlzGene database. A more stringent criteria ( 2.0-fold, p 0.01) identified 94 robustly differentially-expressed proteins. Of these, 72 were modulated by pioglitazone-treatment, with 61% showing the same expressions levels as WT, and 39% showing partial-normalization. 20% of these proteins had known PPRE elements and/or were known responders to pioglitazone. Conclusions: We demonstrated that increased soluble Ab adversely impacts the cerebrovascular proteome. Pioglitazone-mediated functional rescue of the cerebrovasculature is associated with normalization of the majority of altered proteins in the vessel wall, particularly those related to oxidative stress and inflammation.