PXD020251

PXD020251 is an original dataset announced via ProteomeXchange.

Title	High density lipoproteins – a therapeutic target for age-related macular degeneration
Description	We analyzed Apolipoprotein A-1 (ApoA-1) containing lipoproteins isolated from Bruch’s membrane (BrM) of elderly human donor eyes and found a unique proteome, quite different from HDL isolated from donor plasma of the same individuals. The most striking difference is higher concentrations of ApoB and ApoE, which bind to glycosaminoglycans (GAGs). We hypothesize that this interaction promotes lipoprotein deposition onto BrM GAGs, initiating downstream effects that contribute to RPE dysfunction/death. We tested this hypothesis using two therapeutic strategies to alter the lipoprotein/protein profile of these extracellular deposits. First, we used short, heparan sulfate oligosaccharides to remove lipoproteins already deposited in both the extracellular matrix of RPE cells and in aged, donor BrM tissue. Second, we used an ApoA-1 mimetic, 5A peptide, which modulates the relative amounts of cholesterol and ApoA-1, ApoB, and ApoE secreted both apically and basolaterally from primary porcine RPE cells. Significantly, the 5A peptide altered the proteomic profile of circulating HDL and ameliorated some of the potentially harmful changes in protein composition seen with a high fat, high cholesterol diet in a mouse model of AMD. Together, these results indicate that HDL interactions with BrM represent a viable target to slow AMD progression in humans
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:10:30.527.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD020251
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Nikolai Skiba
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-07 16:42:38	ID requested
1	2020-08-11 02:41:23	announced
⏵ 2	2024-10-22 05:10:34	announced	2024-10-22: Updated project metadata.

Kelly UL, Grigsby D, Cady MA, Landowski M, Skiba NP, Liu J, Remaley AT, Klingeborn M, Bowes Rickman C, High-density lipoproteins are a potential therapeutic target for age-related macular degeneration. J Biol Chem, 295(39):13601-13616(2020) [pubmed]

10.6019/PXD020251;

10.1074/jbc.ra119.012305;

submitter keyword: mouse , AMD, PRE cells,human, lipoproteins, Complement factor H

Catherine Bowes Richman
contact affiliation	Duke University, Albert Eye Research Institute
contact email	bowes007@duke.edu
lab head
Nikolai Skiba
contact affiliation	Duke University
contact email	nikolai.skiba@duke.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020251
     1. Label: PRIDE project
     2. Name: High density lipoproteins – a therapeutic target for age-related macular degeneration