Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Amyloid-b inhibits no-cgmp signaling in a cd36- and cd47-dependent manner

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).

Published Version
Available under License : See the attached license file.

Download (640kB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)


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.


Social Networking:
Share |


Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Miller, TW
Isenberg, JSjsi5@pitt.eduJSI5
Shih, HB
Wang, Y
Roberts, DD
ContributionContributors NameEmailPitt UsernameORCID
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


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item