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Article ; Online: 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 / Cantres-Rosario, Yadira M / Carrasquillo-Carrión, Kelvin / Rodríguez-De Jesús, Ana E / Cartagena-Isern, Luz J / García-Requena, Luis A / Roche-Lima, Abiel / Meléndez, Loyda M

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: 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 ...

Abstract	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 activation, oxidative stress, and lysosomal exocytosis. Cannabinoid receptor 2 (CB2R) agonist, JWH-133, decreases 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. MDM were isolated from healthy women donors (
MeSH term(s)	Humans ; Female ; NF-kappa B/metabolism ; Proteomics ; Tandem Mass Spectrometry ; Macrophages/metabolism ; HIV Infections/drug therapy ; HIV Infections/metabolism ; Oxidative Stress ; HIV-1 ; Exocytosis ; Lysosomes/metabolism ; Cannabinoids
Chemical Substances	NF-kappa B ; 1,1-dimethylbutyl-1-deoxy-Delta(9)-THC (TDG8048RDA) ; Cannabinoids
Language	English
Publishing date	2024-03-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25063246
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Article: Inhibition of Cathepsin B and SAPC Secreted by HIV-Infected Macrophages Reverses Common and Unique Apoptosis Pathways

Zenón-Meléndez, Camille N. / Carrasquillo Carrión, Kelvin / Cantres Rosario, Yadira / Roche Lima, Abiel / Meléndez, Loyda M.

Journal of proteome research. 2022 Jan. 07, v. 21, no. 2

2022

Abstract: Human immunodeficiency virus 1 (HIV-1) infects blood monocytes that cross the blood–brain barrier to the central nervous system, inducing neuronal damage. This is prompted by the secretion of viral and neurotoxic factors by HIV-infected macrophages, ... ...

Abstract	Human immunodeficiency virus 1 (HIV-1) infects blood monocytes that cross the blood–brain barrier to the central nervous system, inducing neuronal damage. This is prompted by the secretion of viral and neurotoxic factors by HIV-infected macrophages, resulting in HIV-associated neurocognitive disorders. One of these neurotoxic factors is cathepsin B (CATB), a lysosomal cysteine protease that plays an important role in neurodegeneration. CATB interacts with the serum amyloid P component (SAPC), contributing to HIV-induced neurotoxicity. However, the neuronal apoptosis pathways triggered by CATB and the SAPC remain unknown. We aimed to elucidate these pathways in neurons exposed to HIV-infected macrophage-conditioned media before and after the inhibition of CATB or the SAPC with antibodies using tandem mass tag proteomics labeling. Based on the significant fold change (FC) ≥ \|2\| and p-value < 0.05 criteria, a total of 10, 48, and 13 proteins were deregulated after inhibiting CATB, SAPC antibodies, and the CATB inhibitor CA-074, respectively. We found that neurons exposed to the CATB antibody and SAPC antibody modulate similar proteins (TUBA1A and CYPA/PPIA) and unique proteins (LMNA and HSPH1 for the CATB antibody) or (CFL1 and PFN1 for the SAPC antibody). CATB, SAPC, or apoptosis-related proteins could become potential targets against HIV-induced neuronal degeneration.
Keywords	HIV infections ; Human immunodeficiency virus 1 ; amyloid ; antibodies ; apoptosis ; blood serum ; blood-brain barrier ; cathepsin B ; central nervous system ; macrophages ; monocytes ; neurodegenerative diseases ; neurons ; neurotoxicity ; proteome ; proteomics ; research ; secretion
Language	English
Dates of publication	2022-0107
Size	p. 301-312.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.1c00187
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Inhibition of Cathepsin B and SAPC Secreted by HIV-Infected Macrophages Reverses Common and Unique Apoptosis Pathways.

Zenón-Meléndez, Camille N / Carrasquillo Carrión, Kelvin / Cantres Rosario, Yadira / Roche Lima, Abiel / Meléndez, Loyda M

Journal of proteome research

2022 Volume 21, Issue 2, Page(s) 301–312

Abstract: Human immunodeficiency virus 1 (HIV-1) infects blood monocytes that cross the blood-brain barrier to the central nervous system, inducing neuronal damage. This is prompted by the secretion of viral and neurotoxic factors by HIV-infected macrophages, ... ...

Abstract	Human immunodeficiency virus 1 (HIV-1) infects blood monocytes that cross the blood-brain barrier to the central nervous system, inducing neuronal damage. This is prompted by the secretion of viral and neurotoxic factors by HIV-infected macrophages, resulting in HIV-associated neurocognitive disorders. One of these neurotoxic factors is cathepsin B (CATB), a lysosomal cysteine protease that plays an important role in neurodegeneration. CATB interacts with the serum amyloid P component (SAPC), contributing to HIV-induced neurotoxicity. However, the neuronal apoptosis pathways triggered by CATB and the SAPC remain unknown. We aimed to elucidate these pathways in neurons exposed to HIV-infected macrophage-conditioned media before and after the inhibition of CATB or the SAPC with antibodies using tandem mass tag proteomics labeling. Based on the significant fold change (FC) ≥ \|2\| and
MeSH term(s)	Apoptosis ; Cathepsin B/metabolism ; HIV Infections/metabolism ; Humans ; Macrophages/metabolism ; Profilins/metabolism ; Serum Amyloid P-Component/metabolism
Chemical Substances	PFN1 protein, human ; Profilins ; Serum Amyloid P-Component ; Cathepsin B (EC 3.4.22.1)
Language	English
Publishing date	2022-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.1c00187
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Article ; Online: The Characterization and Evaluation of the Soluble Triggering Receptor Expressed on Myeloid Cells-like Transcript-1 in Stable Coronary Artery Disease.

Bayrón-Marrero, Zaida / Branfield, Siobhan / Menéndez-Pérez, Javier / Nieves-López, Benjamín / Ospina, Laura / Cantres-Rosario, Yadira / Melendez, Loyda M / Hunter, Robert / Gibson, Angelia / Maldonado-Martínez, Gerónimo / Washington, A Valance

International journal of molecular sciences

2023 Volume 24, Issue 17

Abstract: Platelets play crucial roles in the development and progression of coronary artery disease (CAD). The triggering receptor expressed in myeloid cells-like transcript-1 (TLT-1) is stored in platelet α granules, and activated platelets release a soluble ... ...

Abstract	Platelets play crucial roles in the development and progression of coronary artery disease (CAD). The triggering receptor expressed in myeloid cells-like transcript-1 (TLT-1) is stored in platelet α granules, and activated platelets release a soluble fragment (sTLT-1). We set out to better characterize the constituent amino acids of sTLT-1 and to evaluate sTLT-1 for use as a biomarker in patients with stable CAD. We evaluated sTLT-1 release using immunoprecipitation and mass spectrometry and employed statistical methods to retrospectively correlate sTLT-1 concentrations, utilizing ELISA in plasma samples from 1510 patients with documented stable CAD. We identified TLT-1 residues to 133 in platelet releasates. ADAM17 cuts TLT-1, suggesting that S136 is the C-terminal amino acid in sTLT-1. Our results revealed that for CAD patients, sTLT-1 levels did not differ significantly according to primary outcomes of death or major cardiac event; however, patients with left ventricular (LV) dysfunction had significantly lower plasma sTLT-1 levels as compared to those with normal LV function (981.62 ± 1141 pg/mL vs. 1247.48 ± 1589 pg/mL;
MeSH term(s)	Humans ; Coronary Artery Disease/genetics ; Retrospective Studies ; Myeloid Cells ; Blood Platelets ; Amino Acids ; Ventricular Dysfunction, Left
Chemical Substances	Amino Acids
Language	English
Publishing date	2023-09-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241713632
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Article ; Online: Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human Placenta.

Borges-Vélez, Gabriel / Arroyo, Juan A / Cantres-Rosario, Yadira M / Rodriguez de Jesus, Ana / Roche-Lima, Abiel / Rosado-Philippi, Julio / Rosario-Rodríguez, Lester J / Correa-Rivas, María S / Campos-Rivera, Maribel / Meléndez, Loyda M

Cells

2022 Volume 11, Issue 22

Abstract: Zika virus (ZIKV) compromises placental integrity, infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products ...

Abstract	Zika virus (ZIKV) compromises placental integrity, infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor UFO (AXL) have been implicated in ZIKV infection and inflammation. This work investigates CSTB, RAGE, and AXL receptor expression and activation pathways in ZIKV-infected placental tissues at term. The hypothesis is that there is overexpression of CSTB and increased inflammation affecting RAGE and AXL receptor expression in ZIKV-infected placentas. Pathological analyses of 22 placentas were performed to determine changes caused by ZIKV infection. Quantitative proteomics, immunofluorescence, and western blot were performed to analyze proteins and pathways affected by ZIKV infection in frozen placentas. The pathological analysis confirmed decreased size of capillaries, hyperplasia of Hofbauer cells, disruption in the trophoblast layer, cell agglutination, and ZIKV localization to the trophoblast layer. In addition, there was a significant decrease in CSTB, RAGE, and AXL expression and upregulation of caspase 1, tubulin beta, and heat shock protein 27. Modulation of these proteins and activation of inflammasome and pyroptosis pathways suggest targets for modulation of ZIKV infection in the placenta.
MeSH term(s)	Humans ; Female ; Pregnancy ; Zika Virus/physiology ; Zika Virus Infection ; Receptor for Advanced Glycation End Products/metabolism ; Cystatin B/metabolism ; Placenta/metabolism ; Transcription Factors/metabolism ; Inflammation/pathology
Chemical Substances	Receptor for Advanced Glycation End Products ; Cystatin B (88844-95-5) ; Transcription Factors
Language	English
Publishing date	2022-11-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11223627
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Article ; Online: Cannabinoid receptor type 2 agonist JWH-133 decreases cathepsin B secretion and neurotoxicity from HIV-infected macrophages.

Rosario-Rodríguez, Lester J / Gerena, Yamil / García-Requena, Luis A / Cartagena-Isern, Luz J / Cuadrado-Ruiz, Juan C / Borges-Vélez, Gabriel / Meléndez, Loyda M

Scientific reports

2022 Volume 12, Issue 1, Page(s) 233

Abstract: HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy (cART), affecting 52% of people living with HIV. Our laboratory has demonstrated increased expression of cathepsin B (CATB) in postmortem brain tissue ... ...

Abstract	HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy (cART), affecting 52% of people living with HIV. Our laboratory has demonstrated increased expression of cathepsin B (CATB) in postmortem brain tissue with HAND. Increased secretion of CATB from in vitro HIV-infected monocyte-derived macrophages (MDM) induces neurotoxicity. Activation of cannabinoid receptor type 2 (CB2R) inhibits HIV-1 replication in macrophages and the neurotoxicity induced by viral proteins. However, it is unknown if CB2R agonists affect CATB secretion and neurotoxicity in HIV-infected MDM. We hypothesized that HIV-infected MDM exposed to CB2R agonists decrease CATB secretion and neurotoxicity. Primary MDM were inoculated with HIV-1
MeSH term(s)	Apoptosis/drug effects ; Cannabinoids/pharmacology ; Cathepsin B/genetics ; Cathepsin B/metabolism ; Cathepsin B/toxicity ; HIV Infections/complications ; HIV Infections/virology ; HIV-1/physiology ; Humans ; Macrophages/cytology ; Macrophages/drug effects ; Macrophages/metabolism ; Neurocognitive Disorders/etiology ; Neurocognitive Disorders/genetics ; Neurocognitive Disorders/metabolism ; Neurocognitive Disorders/physiopathology ; Neurons/cytology ; Neurons/metabolism ; Receptor, Cannabinoid, CB2/agonists ; Receptor, Cannabinoid, CB2/genetics ; Receptor, Cannabinoid, CB2/metabolism ; Virus Replication/drug effects
Chemical Substances	CNR2 protein, human ; Cannabinoids ; Receptor, Cannabinoid, CB2 ; Cathepsin B (EC 3.4.22.1) ; 1,1-dimethylbutyl-1-deoxy-Delta(9)-THC (TDG8048RDA)
Language	English
Publishing date	2022-01-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-03896-3
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Article ; Online: Cannabinoid receptor type 2 agonist JWH-133 decreases cathepsin B secretion and neurotoxicity from HIV-infected macrophages

Lester J. Rosario-Rodríguez / Yamil Gerena / Luis A. García-Requena / Luz J. Cartagena-Isern / Juan C. Cuadrado-Ruiz / Gabriel Borges-Vélez / Loyda M. Meléndez

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 12

Abstract: Abstract HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy (cART), affecting 52% of people living with HIV. Our laboratory has demonstrated increased expression of cathepsin B (CATB) in postmortem brain ... ...

Abstract	Abstract HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy (cART), affecting 52% of people living with HIV. Our laboratory has demonstrated increased expression of cathepsin B (CATB) in postmortem brain tissue with HAND. Increased secretion of CATB from in vitro HIV-infected monocyte-derived macrophages (MDM) induces neurotoxicity. Activation of cannabinoid receptor type 2 (CB2R) inhibits HIV-1 replication in macrophages and the neurotoxicity induced by viral proteins. However, it is unknown if CB2R agonists affect CATB secretion and neurotoxicity in HIV-infected MDM. We hypothesized that HIV-infected MDM exposed to CB2R agonists decrease CATB secretion and neurotoxicity. Primary MDM were inoculated with HIV-1ADA and treated with selective CB2R agonists JWH-133 and HU-308. HIV-1 p24 and CATB levels were determined from supernatants using ELISA. MDM were pre-treated with a selective CB2R antagonist SR144528 before JWH-133 treatment to determine if CB2R activation is responsible for the effects. Neuronal apoptosis was assessed using a TUNEL assay. Results show that both agonists reduce HIV-1 replication and CATB secretion from MDM in a time and dose-dependent manner and that CB2R activation is responsible for these effects. Finally, JWH-133 decreased HIV/MDM-CATB induced neuronal apoptosis. Our results suggest that agonists of CB2R represent a potential therapeutic strategy against HIV/MDM-induced neurotoxicity.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Erratum: Reduced expression of enolase-1 correlates with high intracellular glucose levels and increased senescence in cisplatin-resistant ovarian cancer cells.

Santana-Rivera, Yasmarie / Rabelo-Fernández, Robert J / Quiñones-Díaz, Blanca I / Grafals-Ruíz, Nilmary / Santiago-Sánchez, Ginette / Lozada-Delgado, Eunice L / Echevarría-Vargas, Ileabett M / Apiz, Juan / Soto, Daniel / Rosado, Andrea / Meléndez, Loyda / Valiyeva, Fatima / Vivas-Mejía, Pablo E

American journal of translational research

2021 Volume 13, Issue 11, Page(s) 13219

Abstract: This corrects the article on p. 1275 in vol. 12, PMID: 32355541.]. ...

Abstract	[This corrects the article on p. 1275 in vol. 12, PMID: 32355541.].
Language	English
Publishing date	2021-11-15
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2471058-1
ISSN	1943-8141
ISSN	1943-8141
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Article ; Online: Dimethyl Fumarate Prevents HIV-Induced Lysosomal Dysfunction and Cathepsin B Release from Macrophages.

Rosario-Rodríguez, Lester J / Colón, Krystal / Borges-Vélez, Gabriel / Negrón, Karla / Meléndez, Loyda M

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

2018 Volume 13, Issue 3, Page(s) 345–354

Abstract: HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy, affecting nearly half of HIV-infected patients worldwide. During HIV infection of macrophages secretion of the lysosomal protein, cathepsin B, is ... ...

Abstract	HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy, affecting nearly half of HIV-infected patients worldwide. During HIV infection of macrophages secretion of the lysosomal protein, cathepsin B, is increased. Secreted cathepsin B has been shown to induce neurotoxicity. Oxidative stress is increased in HIV-infected patients, while antioxidants are decreased in monocytes from patients with HIV-associated dementia (HAD). Dimethyl fumarate (DMF), an antioxidant, has been reported to decrease HIV replication and neurotoxicity mediated by HIV-infected macrophages. Thus, we hypothesized that DMF will decrease cathepsin B release from HIV-infected macrophages by preventing oxidative stress and enhancing lysosomal function. Monocyte-derived macrophages (MDM) were isolated from healthy donors, inoculated with HIV-1
MeSH term(s)	AIDS Dementia Complex/pathology ; Antioxidants/therapeutic use ; Apoptosis/drug effects ; Cathepsin B/metabolism ; Dimethyl Fumarate/therapeutic use ; HIV Core Protein p24/metabolism ; HIV Infections/pathology ; HIV Infections/prevention & control ; HIV-1/drug effects ; Humans ; In Situ Nick-End Labeling ; Macrophages/drug effects ; Macrophages/metabolism ; Oxidative Stress/drug effects ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism ; Virus Replication/drug effects
Chemical Substances	Antioxidants ; HIV Core Protein p24 ; Reactive Nitrogen Species ; Reactive Oxygen Species ; Cathepsin B (EC 3.4.22.1) ; Dimethyl Fumarate (FO2303MNI2)
Language	English
Publishing date	2018-07-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2227405-4
ISSN	1557-1904 ; 1557-1890
ISSN (online)	1557-1904
ISSN	1557-1890
DOI	10.1007/s11481-018-9794-5
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Article ; Online: The COVID-19 Pandemic: Reflections of Science, Person, and Challenge in Academic Research Settings.

Bidlack, Jean M / Chang, Sulie L / Fitting, Sylvia / Gendelman, Howard E / Gorantla, Santhi / Kumar, Santosh / Marcondes, Maria Cecilia Garibaldi / Meigs, Douglas D / Melendez, Loyda M / Sariyer, Ilker K / Yelamanchili, Sowmya

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

2021 Volume 16, Issue 4, Page(s) 706–717

Abstract: ... Drs. Jean M. Bidlack, Sylvia Fitting, Santhi Gorantla, Maria Cecilia G. Marcondes, Loyda M. Melendez ...

Abstract	In spring of 2021, the Society on NeuroImmune Pharmacology (SNIP) organized a virtual workshop on the coronavirus disease 2019 (COVID-19). The daylong event's fourth and final symposium, "Well-being and reflections," offered a glimpse at the pandemic's impact on the lives of our scientists and educators. This manuscript includes a brief summary of the symposium, a transcription of our incoming president Dr. Santosh Kumar's lecture, titled "Intervention and improved well-being of basic science researchers during the COVID-19 era: a case study," and the panel discussion that followed, "Reflection and sharing," featuring Drs. Jean M. Bidlack, Sylvia Fitting, Santhi Gorantla, Maria Cecilia G. Marcondes, Loyda M. Melendez, and Ilker K. Sariyer. The conclusion of this manuscript includes comments from SNIP's president Dr. Sulie L. Chang and our Chief Editor, Dr. Howard E. Gendelman. Drs. Sowmya Yelamanchili and Jeymohan Joseph co-chaired the symposium.
MeSH term(s)	COVID-19 ; Humans ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2021-11-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2227405-4
ISSN	1557-1904 ; 1557-1890
ISSN (online)	1557-1904
ISSN	1557-1890
DOI	10.1007/s11481-021-10035-2
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