Involvement of Insulin-Degrading Enzyme in Insulin- and Atrial Natriuretic Peptide-Sensitive Internalization of Amyloid-β Peptide in Mouse Brain Capillary Endothelial Cells

2013 ◽  
Vol 38 (1) ◽  
pp. 185-200 ◽  
Author(s):  
Shingo Ito ◽  
Sumio Ohtsuki ◽  
Sho Murata ◽  
Yuki Katsukura ◽  
Hiroya Suzuki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Mouse Brain ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Insulin Degrading Enzyme ◽  
Brain Capillary ◽  
Degrading Enzyme ◽  
Capillary Endothelial Cells

Differential expression of selectins by mouse brain capillary endothelial cells in vitro in response to distinct inflammatory stimuli

2006 ◽  
Vol 392 (3) ◽  
pp. 216-220 ◽  
Author(s):  
Caroline Coisne ◽  
Christelle Faveeuw ◽  
Yannick Delplace ◽  
Lucie Dehouck ◽  
Florence Miller ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Differential Expression ◽  
Mouse Brain ◽  
Brain Capillary ◽  
Brain Capillary Endothelial Cells ◽  
Inflammatory Stimuli ◽  
Capillary Endothelial Cells

Localization of norepinephrine and serotonin transporter in mouse brain capillary endothelial cells

2002 ◽  
Vol 44 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Kentaro Wakayama ◽  
Sumio Ohtsuki ◽  
Hitomi Takanaga ◽  
Ken-ichi Hosoya ◽  
Tetsuya Terasaki
Keyword(s):  
Endothelial Cells ◽  
Serotonin Transporter ◽  
Mouse Brain ◽  
Brain Capillary ◽  
Brain Capillary Endothelial Cells ◽  
Capillary Endothelial Cells

scholarly journals The Catalytic Domain of Insulin-degrading Enzyme Forms a Denaturant-resistant Complex with Amyloid β Peptide

2008 ◽  
Vol 283 (25) ◽  
pp. 17039-17048 ◽  
Author(s):  
Ramiro E. Llovera ◽  
Matías de Tullio ◽  
Leonardo G. Alonso ◽  
Malcolm A. Leissring ◽  
Sergio B. Kaufman ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme

scholarly journals Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondria

2004 ◽  
Vol 383 (3) ◽  
pp. 439-446 ◽  
Author(s):  
Malcolm A. LEISSRING ◽  
Wesley FARRIS ◽  
Xining WU ◽  
Danos C. CHRISTODOULOU ◽  
Marcia C. HAIGIS ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Late Onset ◽  
Amyloid Β ◽  
Type Ii Diabetes Mellitus ◽  
Allelic Association ◽  
Amyloid Β Peptide ◽  
Mitochondrial Targeting ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme

IDE (insulin-degrading enzyme) is a widely expressed zinc-metallopeptidase that has been shown to regulate both cerebral amyloid β-peptide and plasma insulin levels in vivo. Genetic linkage and allelic association have been reported between the IDE gene locus and both late-onset Alzheimer's disease and Type II diabetes mellitus, suggesting that altered IDE function may contribute to some cases of these highly prevalent disorders. Despite the potentially great importance of this peptidase to health and disease, many fundamental aspects of IDE biology remain unresolved. Here we identify a previously undescribed mitochondrial isoform of IDE generated by translation at an in-frame initiation codon 123 nucleotides upstream of the canonical translation start site, which results in the addition of a 41-amino-acid N-terminal mitochondrial targeting sequence. Fusion of this sequence to the N-terminus of green fluorescent protein directed this normally cytosolic protein to mitochondria, and full-length IDE constructs containing this sequence were also directed to mitochondria, as revealed by immuno-electron microscopy. Endogenous IDE protein was detected in purified mitochondria, where it was protected from digestion by trypsin and migrated at a size consistent with the predicted removal of the N-terminal targeting sequence upon transport into the mitochondrion. Functionally, we provide evidence that IDE can degrade cleaved mitochondrial targeting sequences. Our results identify new mechanisms regulating the subcellular localization of IDE and suggest previously unrecognized roles for IDE within mitochondria.

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