Insulin degrading enzyme is localized predominantly at the cell surface of polarized and unpolarized human cerebrovascular endothelial cell cultures

@article{Lynch2006InsulinDE,
  title={Insulin degrading enzyme is localized predominantly at the cell surface of polarized and unpolarized human cerebrovascular endothelial cell cultures},
  author={John A Lynch and Ana George and Patricia B. Eisenhauer and Kelly J. Conn and Wenwu Gao and Isabel Carreras and John M. Wells and Ann C. McKee and M. David Ullman and Richard E. Fine},
  journal={Journal of Neuroscience Research},
  year={2006},
  volume={83}
}
Insulin degrading enzyme (IDE) is expressed in the brain and may play an important role there in the degradation of the amyloid beta peptide (Aβ). Our results show that cultured human cerebrovascular endothelial cells (HCECs), a primary component of the blood–brain barrier, express IDE and may respond to exposure to low levels of Aβ by upregulating its expression. When radiolabeled Aβ is introduced to the medium of cultured HCECs, it is rapidly degraded to smaller fragments. We believe that… 
Detergent resistant membrane-associated IDE in brain tissue and cultured cells: Relevance to Aβ and insulin degradation
TLDR
The results support the notion that optimal substrate degradation by IDE may require its association with organized-DRMs, and the concept that mis-location of Aβ degrading proteases away from DRMs may impair the physiological turn-over of A β in vivo deserves further investigation.
Characterization of insulin degrading enzyme and other amyloid-β degrading proteases in human serum: a role in Alzheimer's disease?
TLDR
The elderly with probable AD had lower serum substrate V degradation activity compared with those who had vascular dementia, and the blood proteases mediating Aβ degradation may be important for the AD pathogenesis.
Aβ degradation or cerebral perfusion? Divergent effects of multifunctional enzymes
TLDR
Assessing the role of Aβ-degrading proteases in the pathogenesis of AD and, particularly, their potential as therapeutic agents, it is important to bear in mind the multifunctional nature of these enzymes and to consider their effects on other substrates and pathways.
Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic peptide-sensitive internalization of amyloid-β peptide in mouse brain capillary endothelial cells.
TLDR
It is concluded that elimination of hAβ1-40 from mouse brain across the BBB involves an insulin- and ANP-sensitive process, mediated by IDE expressed in brain capillary endothelial cells.
Degradation of Relaxin Family Peptides by Insulin‐Degrading Enzyme
TLDR
It is determined that relaxin, relaxin‐3, and InsL3 all competitively inhibited the degradation of insulin by IDE to different degrees, and all inhibited covalent cross‐linking of insulin to IDE.
The insulin receptor is expressed and functional in cultured blood-brain barrier endothelial cells but does not mediate insulin entry from blood to brain.
TLDR
In vitro data indicate that peripheral insulin must reach the brain parenchyma through alternative pathways rather than crossing the blood-brain barrier via receptor mediated transcytosis.
Down‐regulation of insulin‐degrading enzyme by presenilin 1 V97L mutant potentially underlies increased levels of amyloid beta 42
  • W. Qin, J. Jia
  • Biology
    The European journal of neuroscience
  • 2008
TLDR
These studies indicate that pathological levels of Aβ42 may be caused by the negative effects of PS1 (V97L) on IDE expression and activity, and provide evidence for the molecular basis of familial Alzheimer's disease pathogenesis.
Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues.
TLDR
A wide-ranging survey on IDE protein expression in normal and malignant tissues and cells is performed for the first time, extending knowledge on the cellular and tissue distribution of IDE.
...
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References

SHOWING 1-10 OF 65 REFERENCES
Insulin-degrading Enzyme Regulates Extracellular Levels of Amyloid β-Protein by Degradation*
TLDR
It is concluded that a principal protease capable of down-regulating the levels of secreted Aβ extracellularly is IDE, and activity was unexpectedly found be associated with a time-dependent oligomerization of synthetic Aβ at physiological levels in the conditioned media of cultured cells.
Neurons Regulate Extracellular Levels of Amyloid β-Protein via Proteolysis by Insulin-Degrading Enzyme
TLDR
A principal role for membrane-associated and secreted IDE isoforms in the degradation and clearance of naturally secreted Aβ by neurons and microglia is supported.
Insulin-degrading enzyme.
TLDR
It is proposed that insulin-degrading enzyme (IDE), an evolutionarily conserved, neutral thiol-metalloendopeptidase, plays a crucial role in the degradation of internalized insulin in many types of cells and must have important functions and multifaceted biological significance.
Degradation of Insulin by Isolated Mouse Pancreatic Acini: Evidence for Cell Surface Protease Activity
TLDR
The data indicated that 125I-insulin degradation by acini occurred primarily via nonreceptor mechanisms, and that insulin degradation was inhibited by thiolreacting agents such as N-ethylmaleimide and p-chloromercuribenzoate.
Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo
TLDR
In vivo findings suggest that IDE hypofunction may underlie or contribute to some forms of AD and DM2 and provide a mechanism for the recently recognized association among hyperinsulinemia, diabetes, and AD.
Insulin-degrading Enzyme in Brain Microvessels
TLDR
The notion that a defect in Aβ proteolysis by IDE contributes to the accumulation of this peptide in the cortical microvasculature is supported and the possibility that IDE inhibition or inactivation is a pathogenic mechanism that may open novel strategies for the treatment of cerebrovascular Aβ amyloidoses is raised.
Degradation of Amylin by Insulin-degrading Enzyme*
TLDR
The data strongly suggest that IDE is an amylin-degrading enzyme and plays an important role in the clearance ofAmylin and the prevention of islet amyloid formation.
Cellular localization of insulin-degrading enzyme in rat liver using monoclonal antibodies specific for this enzyme.
Inhibition of insulin-degrading enzyme increases translocation of insulin to the nucleus in H35 rat hepatoma cells: evidence of a cytosolic pathway.
TLDR
The results suggested that inhibition of cytosolic IDE activity resulted in increased insulin translocation from the cytosol to the nucleus, and the IDE regulatory mechanism could play a crucial role in insulin's regulation of gene expression and cell proliferation.
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