Limits...
Impact of age on the cerebrovascular proteomes of wild-type and Tg-SwDI mice.

Searcy JL, Le Bihan T, Salvadores N, McCulloch J, Horsburgh K - PLoS ONE (2014)

Bottom Line: The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis.Sixty-five proteins were significantly increased in older WT animals and included several basement membrane proteins (nidogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, laminin subunit gamma-1 precursor and collagen alpha-2(IV) chain preproprotein).Of these, increases in Apolipoprotein E (APOE) and high temperature requirement serine protease-1 (HTRA1) and decreases in spliceosome and RNA-binding proteins were the most prominent.

View Article: PubMed Central - PubMed

Affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT
The structural integrity of cerebral vessels is compromised during ageing. Abnormal amyloid (Aβ) deposition in the vasculature can accelerate age-related pathologies. The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis. Over 650 proteins were quantified in vessel-enriched fractions from the brains of 3 and 9 month-old wild-type (WT) and Tg-SwDI mice. Sixty-five proteins were significantly increased in older WT animals and included several basement membrane proteins (nidogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, laminin subunit gamma-1 precursor and collagen alpha-2(IV) chain preproprotein). Twenty-four proteins were increased and twenty-one decreased in older Tg-SwDI mice. Of these, increases in Apolipoprotein E (APOE) and high temperature requirement serine protease-1 (HTRA1) and decreases in spliceosome and RNA-binding proteins were the most prominent. Only six shared proteins were altered in both 9-month old WT and Tg-SwDI animals. The age-related proteomic response in the cerebrovasculature was distinctly different in the presence of microvascular Aβ deposition. Proteins found differentially expressed within the WT and Tg-SwDI animals give greater insight to the mechanisms behind age-related cerebrovascular dysfunction and pathologies and may provide novel therapeutic targets.

Show MeSH

Related in: MedlinePlus

Age effects on the Tg-SwDI vascular proteome.Multiple heterogeneous nuclear ribonucleoproteins were down-regulated in 9 month-old Tg-SwDI animals (Mean abundance ± S.E.M; ***p<.001; **p<0.01; t-test) compared to younger animals. No significant difference was observed in the WT cohort.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3935958&req=5

pone-0089970-g006: Age effects on the Tg-SwDI vascular proteome.Multiple heterogeneous nuclear ribonucleoproteins were down-regulated in 9 month-old Tg-SwDI animals (Mean abundance ± S.E.M; ***p<.001; **p<0.01; t-test) compared to younger animals. No significant difference was observed in the WT cohort.

Mentions: Age led to the extensive down-regulation of several proteins associated with the spliceosome (note figure 3) and RNA processing in the Tg-SwDI animals based on gene ontology (biological process; Figure S3). These include several members of the heterogeneous nuclear ribonucleoprotein family of proteins (Figure 6).


Impact of age on the cerebrovascular proteomes of wild-type and Tg-SwDI mice.

Searcy JL, Le Bihan T, Salvadores N, McCulloch J, Horsburgh K - PLoS ONE (2014)

Age effects on the Tg-SwDI vascular proteome.Multiple heterogeneous nuclear ribonucleoproteins were down-regulated in 9 month-old Tg-SwDI animals (Mean abundance ± S.E.M; ***p<.001; **p<0.01; t-test) compared to younger animals. No significant difference was observed in the WT cohort.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935958&req=5

pone-0089970-g006: Age effects on the Tg-SwDI vascular proteome.Multiple heterogeneous nuclear ribonucleoproteins were down-regulated in 9 month-old Tg-SwDI animals (Mean abundance ± S.E.M; ***p<.001; **p<0.01; t-test) compared to younger animals. No significant difference was observed in the WT cohort.
Mentions: Age led to the extensive down-regulation of several proteins associated with the spliceosome (note figure 3) and RNA processing in the Tg-SwDI animals based on gene ontology (biological process; Figure S3). These include several members of the heterogeneous nuclear ribonucleoprotein family of proteins (Figure 6).

Bottom Line: The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis.Sixty-five proteins were significantly increased in older WT animals and included several basement membrane proteins (nidogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, laminin subunit gamma-1 precursor and collagen alpha-2(IV) chain preproprotein).Of these, increases in Apolipoprotein E (APOE) and high temperature requirement serine protease-1 (HTRA1) and decreases in spliceosome and RNA-binding proteins were the most prominent.

View Article: PubMed Central - PubMed

Affiliation: Centre for Neuroregeneration, University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT
The structural integrity of cerebral vessels is compromised during ageing. Abnormal amyloid (Aβ) deposition in the vasculature can accelerate age-related pathologies. The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis. Over 650 proteins were quantified in vessel-enriched fractions from the brains of 3 and 9 month-old wild-type (WT) and Tg-SwDI mice. Sixty-five proteins were significantly increased in older WT animals and included several basement membrane proteins (nidogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, laminin subunit gamma-1 precursor and collagen alpha-2(IV) chain preproprotein). Twenty-four proteins were increased and twenty-one decreased in older Tg-SwDI mice. Of these, increases in Apolipoprotein E (APOE) and high temperature requirement serine protease-1 (HTRA1) and decreases in spliceosome and RNA-binding proteins were the most prominent. Only six shared proteins were altered in both 9-month old WT and Tg-SwDI animals. The age-related proteomic response in the cerebrovasculature was distinctly different in the presence of microvascular Aβ deposition. Proteins found differentially expressed within the WT and Tg-SwDI animals give greater insight to the mechanisms behind age-related cerebrovascular dysfunction and pathologies and may provide novel therapeutic targets.

Show MeSH
Related in: MedlinePlus