The Hippocampal Proteomic Analysis of Senescence-Accelerated Mouse: Implications of Uchl3 and Mitofilin in Cognitive Disorder and Mitochondria Dysfunction in SAMP8

Abstract

Senescence-accelerated mouse prone 8 (SAMP8) is considered as a useful animal model for age-related learning and memory impairments. Hippocampus, a critical brain region associated with cognitive decline during normal aging and various neurodegenerative diseases, appeared a series of abnormalities in SAMP8. To investigate the molecular mechanisms underlying age-related cognitive disorders, we used 2-DE coupled with MALDI TOF/TOF MS to analyze the differential protein expression of the hippocampus of SAMP8 at 6-month-old compared with the age-matched SAM/resistant 1 (SAMR1) which shows normal aging process. Two proteins were found to be markedly changed in SAMP8 as compared to SAMR1: ubiquitin carboxyl-terminal hydrolase L3 (Uchl3), implicating in cytosolic proteolysis of oxidatively damaged proteins, was down-regulated while mitofilin, a vital protein for normal mitochondria function, exhibited four isoforms with a consistent basic shift of isoelectric point among the soluble hippocampal proteins in SAMP8 compared with SAMR1. The alterations were confirmed by Western blotting analysis. The analysis of their expression changes may shed light on the mechanisms of learning and memory deficits and mitochondrial dysfunction as observed in SAMP8.

Transgenic overexpression of mitofilin attenuates diabetes mellitus-associated cardiac and mitochondria dysfunction

“…Moreover, two different models of cardiomyopathy were being studied; diabetic cardiomyopathy and hypertrophy that depict a differential expression of mitofilin levels suggesting its distinct role in these pathologies. Furthermore, decrements in mitofilin content have also been observed in other human diseases such as Down’s syndrome [24, 25], Parkinson’s disease [26, 27], Epilepsy [28, 29] and Neurodegeneration [30, 31]. Hence, these varied changes of mitofilin observed in different human pathologies as well as different cardiac pathologies suggest unique responses and effects of mitofilin under different pathological stimuli.…”

“…Decrements in mitofilin content have been observed in many human diseases such as Down’s syndrome [24, 25], Parkinson’s disease [26, 27], Epilepsy [28, 29] and Neurodegeneration [30, 31]. Abnormal mitochondrial morphology, significant reduction in cristae density, as well as decrements in mitofilin content have been reported in the type 1 diabetic heart [32, 33].…”

Mitofilin complexes: conserved organizers of mitochondrial membrane architecture

“…(iii) Mitofilin levels were decreased in heart muscle mitochondria in a mouse model for diabetic cardiomyopathy (Baseler et al , 2011 ). (iv) Alterations of mitofilin have been described in different animal models for neurodegeneration (Wishart et al , 2007 ;Wang et al , 2008 ;McDonald et al , 2009 ). (v) Oxidative damage as well as altered mitofilin levels have been found in model systems of Parkinson ' s disease (van Laar et al , 2007(van Laar et al , , 2009Burt é et al, 2011 ).…”

Differential Proteomics Analysis of Specific Carbonylated Proteins in the Temporal Cortex of Aged Rats: The Deterioration of Antioxidant System

“…Two dimensional electrophoresis was performed as previously described with minor modifications [28,29]. Just prior to the first dimension of 2-DE, the aliquoted sample containing 300 lg (for Western blotting) or 800 lg (for mass identification) protein was diluted to 250 ll with rehydration buffer and supplemented with 0.5% IPG buffer (pH 3-10 NL, GE Healthcare, Sweden).…”