Dataset Information

Quantitative proteomics reveal that CB2R agonist JWH-133 downregulates NF-κB activation, oxidative stress, and lysosomal exocytosis from HIV-infected macrophages

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood, Macrophage

DISEASE(S): Human Immunodeficiency Virus Infectious Disease

SUBMITTER: Loyda Melendez

LAB HEAD: Loyda Melendez

PROVIDER: PXD048464 | Pride | 2024-06-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	LesterRosario_TMTAnalysis1_18Dic2023.msf	Msf
	LesterRosario_TMTAnalysis1_18Dic2023.mzML	Mzml
	LesterRosario_TMTAnalysis1_18Dic2023.mzid.gz	Mzid
	TMT_Pool1_Fraction1_Lester_27Jul2020.raw	Raw
	TMT_Pool1_Fraction2_Lester_27Jul2020.raw	Raw

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Publications

Quantitative Proteomics Reveal That CB2R Agonist JWH-133 Downregulates NF-κB Activation, Oxidative Stress, and Lysosomal Exocytosis from HIV-Infected Macrophages.

Rosario-Rodríguez Lester J LJ Cantres-Rosario Yadira M YM Carrasquillo-Carrión Kelvin K Rodríguez-De Jesús Ana E AE Cartagena-Isern Luz J LJ García-Requena Luis A LA Roche-Lima Abiel A Meléndez Loyda M LM

International journal of molecular sciences 20240313 6

HIV-associated neurocognitive disorders (HAND) affect 15-55% of HIV-positive patients and effective therapies are unavailable. HIV-infected monocyte-derived macrophages (MDM) invade the brain of these individuals, promoting neurotoxicity. We demonstrated an 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 their secretion is associated with NF-κB ...[more]

PMID: 38542221

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