Quantitative proteomics analysis of specific protein expression and oxidative modification in aged senescence-accelerated-prone 8 mice brain.
The senescence-accelerated mouse (SAM) is a murine model of accelerated senescence that was established using phenotypic selection. The SAMP series includes nine substrains, each of which exhibits characteristic disorders. SAMP8 is known to exhibit age-dependent learning and memory deficits. In our previous study, we reported that brains from 12-month-old SAMP8 have greater protein oxidation, as well as lipid peroxidation, compared with brains from 4-month-old SAMP8 mice. In order to investigate the relation between age-associated oxidative stress on specific protein oxidation and age-related learning and memory deficits in SAMP8, we used proteomics to identify proteins that are expressed differently and/or modified oxidatively in aged SAMP8 brains. We report here that in 12 month SAMP8 mice brains the expressions of neurofilament triplet L protein, lactate dehydrogenase 2 (LDH-2), heat shock protein 86, and alpha-spectrin are significantly decreased, while the expression of triosephosphate isomerase (TPI) is increased compared with 4-month-old SAMP8 brains. We also report that the specific protein carbonyl levels of LDH-2, dihydropyrimidinase-like protein 2, alpha-spectrin and creatine kinase, are significantly increased in the brain of 12-month-old SAMP8 mice when compared with the 4-month-old SAMP8 brain. These findings are discussed in reference to the effect of specific protein oxidation and changes of expression on potential mechanisms of abnormal alterations in metabolism and neurochemicals, as well as to the learning and memory deficits in aged SAMP8 mice.
Poon
H F
HF
Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA.
Castegna
A
A
Farr
S A
SA
Thongboonkerd
V
V
Lynn
B C
BC
Banks
W A
WA
Morley
J E
JE
Klein
J B
JB
Butterfield
D A
DA
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D008818:Mice, Neurologic Mutants; D018384:Oxidative Stress / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods
D011506:Proteins