Potential roles for presenilin-1 in oxygen sensing and in glial-specific gene expression.
The integral membrane glycoprotein presenilin-1 (PS1), in concert with beta-secretase and beta amyloid precursor protein (betaAPP), orchestrate cleavage of betaAPP into amyloidogenic Abeta 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 betaAPP and hypoxia inducible factor-1 alpha (HIF-1alpha), and a marked up-regulation in the expression of glial-specific markers that include S100beta 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.
Neuroscience Center and Department of Ophthalmology, Louisiana State University, 2020 Gravier Street, New Orleans, LA 70112, USA.
Jian-Guo
JG
Cui
Paul E
PE
Fraser
Peter
P
St George-Hyslop
David
D
Westaway
Walter J
WJ
Lukiw
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010100:Oxygen / Q000378:metabolism*; D053764:Presenilin-1; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012313:RNA; D010100:Oxygen