Potential roles for presenilin-1 in oxygen sensing and in glial-specific gene expression

Jian Guo Cui; Paul E. Fraser; Peter St. George-Hyslop; David Westaway; Walter J. Lukiw

doi:10.1097/00001756-200409150-00006

Potential roles for presenilin-1 in oxygen sensing and in glial-specific gene expression

Jian Guo Cui, Paul E. Fraser, Peter St. George-Hyslop, David Westaway, Walter J. Lukiw

Anesthesiology

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

The integral membrane glycoprotein presenilin-1 (PS1), in concert with β-secretase and beta amyloid precursor protein (βAPP), orchestrate cleavage of βAPP into amyloidogenic Aβ peptides.To gain further insight into PS1 function, we undertook a gene expression profiling study that interrogated the expression of 12 000 genes in the forebrain of PS1-hypomorphic mice that exhibit highly attenuated PS1 activity. Using stringent RNA screening, DNA array and Northern assay, we report significant down-regulation in the expression of βAPP and hypoxia inducible factor-1 alpha (HIF-1α), and a marked up-regulation in the expression of glial-specific markers that include S100β protein, glycerol phosphate dehydrogenase, and glial fibrillary acidic protein. These data suggest potential roles for PS1 in the cellular response to hypoxia and glial-specific gene expression.

Original language	English (US)
Pages (from-to)	2025-2028
Number of pages	4
Journal	Neuroreport
Volume	15
Issue number	13
DOIs	https://doi.org/10.1097/00001756-200409150-00006
State	Published - Sep 1 2004

Keywords

Aβ peptides
Alzheimer's disease
Glial fibrillary acidic protein
Gliosis
Glycerol phosphate dehydrogenase
Hypomorphic mice
Hypoxia inducible factor 1 alpha
S100β protein

ASJC Scopus subject areas

Neuroscience(all)

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10.1097/00001756-200409150-00006

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title = "Potential roles for presenilin-1 in oxygen sensing and in glial-specific gene expression",

abstract = "The integral membrane glycoprotein presenilin-1 (PS1), in concert with β-secretase and beta amyloid precursor protein (βAPP), orchestrate cleavage of βAPP into amyloidogenic Aβ peptides.To gain further insight into PS1 function, we undertook a gene expression profiling study that interrogated the expression of 12 000 genes in the forebrain of PS1-hypomorphic mice that exhibit highly attenuated PS1 activity. Using stringent RNA screening, DNA array and Northern assay, we report significant down-regulation in the expression of βAPP and hypoxia inducible factor-1 alpha (HIF-1α), and a marked up-regulation in the expression of glial-specific markers that include S100β protein, glycerol phosphate dehydrogenase, and glial fibrillary acidic protein. These data suggest potential roles for PS1 in the cellular response to hypoxia and glial-specific gene expression.",

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AU - Fraser, Paul E.

AU - St. George-Hyslop, Peter

AU - Westaway, David

AU - Lukiw, Walter J.

PY - 2004/9/1

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AB - The integral membrane glycoprotein presenilin-1 (PS1), in concert with β-secretase and beta amyloid precursor protein (βAPP), orchestrate cleavage of βAPP into amyloidogenic Aβ peptides.To gain further insight into PS1 function, we undertook a gene expression profiling study that interrogated the expression of 12 000 genes in the forebrain of PS1-hypomorphic mice that exhibit highly attenuated PS1 activity. Using stringent RNA screening, DNA array and Northern assay, we report significant down-regulation in the expression of βAPP and hypoxia inducible factor-1 alpha (HIF-1α), and a marked up-regulation in the expression of glial-specific markers that include S100β protein, glycerol phosphate dehydrogenase, and glial fibrillary acidic protein. These data suggest potential roles for PS1 in the cellular response to hypoxia and glial-specific gene expression.

KW - Aβ peptides

KW - Alzheimer's disease

KW - Glial fibrillary acidic protein

KW - Gliosis

KW - Glycerol phosphate dehydrogenase

KW - Hypomorphic mice

KW - Hypoxia inducible factor 1 alpha

KW - S100β protein

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Potential roles for presenilin-1 in oxygen sensing and in glial-specific gene expression

Abstract

Keywords

ASJC Scopus subject areas

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