PXD048464

PXD048464 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomics reveal that CB2R agonist JWH-133 downregulates NF-κB activation, oxidative stress, and lysosomal exocytosis from HIV-infected macrophages
Description	HIV-associated neurocognitive disorders (HAND) affect 15-55% of HIV-positive patients, with no therapy. HIV-infected monocyte-derived macrophages (MDM) invade the brain of these individuals, promoting neurotoxicity. We demonstrated increased expression of cathepsin B (CATB), a lysosomal protease, in monocytes and post-mortem brain tissues of women with HAND. Increased CATB release from HIV-infected MDM leads to neurotoxicity, and its secretion is associated with NF-κB activation, oxidative stress, and lysosomal exocytosis. Cannabinoid receptor 2 (CB2R) agonist, JWH-133, was shown to decrease HIV-1 replication, CATB secretion, and neurotoxicity from HIV-infected MDM but the mechanisms are not entirely understood. We hypothesized that HIV-1 infection upregulates the expression of proteins associated with oxidative stress and that a CB2R agonist could reverse these effects. To test our hypothesis MDM were isolated from healthy women donors (n=3), infected with HIV-1ADA, and treated with JWH-133. After 13 days post-infection cell lysates were labeled by Tandem Mass Tags (TMT) and analyzed by LC/MS/MS quantitative proteomics bioinformatics. While HIV-1 infection upregulated CATB, NF-κB signaling, Nrf2-mediated oxidative stress response, and lysosomal exocytosis, JWH-133 treatment downregulated their expression. Our results suggest that JWH-133 is a potential alternative therapy against HIV-1 induced neurotoxicity and warrant in vivo studies to test its potential against HAND.
HostingRepository	PRIDE
AnnounceDate	2024-06-22
AnnouncementXML	Submission_2024-06-22_08:34:13.847.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD048464
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Loyda Melendez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-11 08:44:59	ID requested
⏵ 1	2024-06-22 08:34:14	announced

Rosario-Rodr, í, guez LJ, Cantres-Rosario YM, Carrasquillo-Carri, ó, n K, Rodr, í, guez-De Jes, ú, s AE, Cartagena-Isern LJ, Garc, í, a-Requena LA, Roche-Lima A, Mel, é, ndez LM, B Activation, Oxidative Stress, and Lysosomal Exocytosis from HIV-Infected Macrophages. Int J Mol Sci, 25(6):(2024) [pubmed]

10.3390/ijms25063246;

10.6019/PXD048464;

submitter keyword: proteomics, Human, macrophages, neurotoxicity, oxidative stress, HIV, HAND, CB2R, cathepsin B

Loyda Melendez
contact affiliation	University of Puerto Rico, Medical Sciences Campus, Translational Proteomics Center
contact email	lmelendezlab@gmail.com
lab head
Loyda Melendez
contact affiliation	University of Puerto Rico Medical Sciences Campus
contact email	lmelendezlab@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048464
     1. Label: PRIDE project
     2. Name: Quantitative proteomics reveal that CB2R agonist JWH-133 downregulates NF-κB activation, oxidative stress, and lysosomal exocytosis from HIV-infected macrophages