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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.

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Proteomic design and workflow.(A) Vessel enriched fractions were collected from 3 month-old and 9 month-old WT and 3 month-old and 9 month-old Tg-SwDI mice for proteomic analysis. (B) Over 1,000 proteins were identified, with over 70% being identified by more than two peptides. 654 proteins were quantified by at least two peptides and were statistically analysed using Progenesis software. 65 proteins were found to be up-regulated in the WT animals. 45 proteins were found to be up- and down-regulated (21 and 24 respectively) in the Tg-SwDI animals. Those proteins that were found to be significantly different within the respective cohorts were analysed further with WebGestalt web-based software.
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pone-0089970-g002: Proteomic design and workflow.(A) Vessel enriched fractions were collected from 3 month-old and 9 month-old WT and 3 month-old and 9 month-old Tg-SwDI mice for proteomic analysis. (B) Over 1,000 proteins were identified, with over 70% being identified by more than two peptides. 654 proteins were quantified by at least two peptides and were statistically analysed using Progenesis software. 65 proteins were found to be up-regulated in the WT animals. 45 proteins were found to be up- and down-regulated (21 and 24 respectively) in the Tg-SwDI animals. Those proteins that were found to be significantly different within the respective cohorts were analysed further with WebGestalt web-based software.

Mentions: 1024 proteins were identified within the S1 fractions from young and older WT and Tg-SwDI mice. 654 were quantified by at least 2 peptides across all groups (a list of all proteins quantified by 2 peptides can be found in Table S1). The proteomic workflow along with a summary of results is presented (Figure 2).


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)

Proteomic design and workflow.(A) Vessel enriched fractions were collected from 3 month-old and 9 month-old WT and 3 month-old and 9 month-old Tg-SwDI mice for proteomic analysis. (B) Over 1,000 proteins were identified, with over 70% being identified by more than two peptides. 654 proteins were quantified by at least two peptides and were statistically analysed using Progenesis software. 65 proteins were found to be up-regulated in the WT animals. 45 proteins were found to be up- and down-regulated (21 and 24 respectively) in the Tg-SwDI animals. Those proteins that were found to be significantly different within the respective cohorts were analysed further with WebGestalt web-based software.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0089970-g002: Proteomic design and workflow.(A) Vessel enriched fractions were collected from 3 month-old and 9 month-old WT and 3 month-old and 9 month-old Tg-SwDI mice for proteomic analysis. (B) Over 1,000 proteins were identified, with over 70% being identified by more than two peptides. 654 proteins were quantified by at least two peptides and were statistically analysed using Progenesis software. 65 proteins were found to be up-regulated in the WT animals. 45 proteins were found to be up- and down-regulated (21 and 24 respectively) in the Tg-SwDI animals. Those proteins that were found to be significantly different within the respective cohorts were analysed further with WebGestalt web-based software.
Mentions: 1024 proteins were identified within the S1 fractions from young and older WT and Tg-SwDI mice. 654 were quantified by at least 2 peptides across all groups (a list of all proteins quantified by 2 peptides can be found in Table S1). The proteomic workflow along with a summary of results is presented (Figure 2).

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