Miller, TW and Isenberg, JS and Shih, HB and Wang, Y and Roberts, DD
(2010)
Amyloid-b inhibits no-cgmp signaling in a cd36- and cd47-dependent manner.
PLoS ONE, 5 (12).
Abstract
Amyloid-b interacts with two cell surface receptors, CD36 and CD47, through which the matricellular protein thrombospondin-1 inhibits soluble guanylate cyclase activation. Here we examine whether amyloid-b shares this inhibitory activity. Amyloid-b inhibited both drug and nitric oxide-mediated activation of soluble guanylate cyclase in several cell types. Known cGMP-dependent functional responses to nitric oxide in platelets and vascular smooth muscle cells were correspondingly inhibited by amyloid-b. Functional interaction of amyloid-b with the scavenger receptor CD36 was indicated by inhibition of free fatty acid uptake via this receptor. Both soluble oligomer and fibrillar forms of amyloid-b were active. In contrast, amyloid-b did not compete with the known ligand SIRPa for binding to CD47. However, both receptors were necessary for amyloid-b to inhibit cGMP accumulation. These data suggest that amyloid-b interaction with CD36 induces a CD47-dependent signal that inhibits soluble guanylate cyclase activation. Combined with the pleiotropic effects of inhibiting free fatty acid transport via CD36, these data provides a molecular mechanism through which amyloid-b can contribute to the nitric oxide signaling deficiencies associated with Alzheimer's disease.
Share
Citation/Export: |
|
Social Networking: |
|
Details
Item Type: |
Article
|
Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
---|
Miller, TW | | | | Isenberg, JS | jsi5@pitt.edu | JSI5 | | Shih, HB | | | | Wang, Y | | | | Roberts, DD | | | |
|
Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID  |
---|
Editor | Ferreira, Sergio T. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
|
Date: |
1 December 2010 |
Date Type: |
Publication |
Journal or Publication Title: |
PLoS ONE |
Volume: |
5 |
Number: |
12 |
DOI or Unique Handle: |
10.1371/journal.pone.0015686 |
Refereed: |
Yes |
MeSH Headings: |
Amyloid beta-Peptides--metabolism; Animals; Antigens, CD36--biosynthesis; Antigens, CD47--biosynthesis; Aorta--cytology; Cattle; Cyclic GMP--metabolism; Endothelial Cells--cytology; Humans; Mice; Nitric Oxide--metabolism; Protein Conformation; Pyrazoles--pharmacology; Pyridines--pharmacology; Signal Transduction; Swine; Umbilical Veins--cytology |
Other ID: |
NLM PMC3008726 |
PubMed Central ID: |
PMC3008726 |
PubMed ID: |
21203512 |
Date Deposited: |
25 Aug 2012 16:41 |
Last Modified: |
25 Jan 2019 21:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/13667 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Altmetric.com
Actions (login required)
 |
View Item |