دورية أكاديمية
HIV Increases the Inhibitory Impact of Morphine and Antiretrovirals on Autophagy in Primary Human Macrophages: Contributions to Neuropathogenesis.
العنوان: | HIV Increases the Inhibitory Impact of Morphine and Antiretrovirals on Autophagy in Primary Human Macrophages: Contributions to Neuropathogenesis. |
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المؤلفون: | Barbaro JM; Montefiore Medical Center, Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA., Cuervo AM; Montefiore Medical Center, Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA., Berman JW; Montefiore Medical Center, Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.; Montefiore Medical Center, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA. |
المصدر: | Cells [Cells] 2021 Aug 24; Vol. 10 (9). Date of Electronic Publication: 2021 Aug 24. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI |
مواضيع طبية MeSH: | Anti-Retroviral Agents/*pharmacology , Autophagy/*drug effects , HIV Infections/*drug therapy , Macrophages/*drug effects , Morphine/*pharmacology , Neurocognitive Disorders/*drug therapy, Cells, Cultured ; HIV Infections/virology ; HIV-1/pathogenicity ; Humans ; Mitophagy/drug effects ; Neurocognitive Disorders/virology |
مستخلص: | HIV enters the CNS early after peripheral infection, establishing reservoirs in perivascular macrophages that contribute to development of HIV-associated neurocognitive disorders (HAND) in 15-40% of people with HIV (PWH) despite effective antiretroviral therapy (ART). Opioid use may contribute to dysregulated macrophage functions resulting in more severe neurocognitive symptoms in PWH taking opioids. Macroautophagy helps maintain quality control in long-lived cell types, such as macrophages, and has been shown to regulate, in part, some macrophage functions in the CNS that contribute to HAND. Using Western blotting and confocal immunofluorescence in primary human macrophages, we demonstrated that morphine and a commonly prescribed ART regimen induce bulk autophagy. Morphine and ART also inhibited completion of autophagy. HIV infection increased these inhibitory effects. We also examined two types of selective autophagy that degrade aggregated proteins (aggrephagy) and dysfunctional mitochondria (mitophagy). Morphine and ART inhibited selective autophagy mediated by p62 regardless of HIV infection, and morphine inhibited mitophagic flux in HIV-infected cells demonstrating potential mitotoxicity. These results indicate that inhibition of autophagy, both in bulk and selective, in CNS macrophages may mediate neurocognitive dysfunction in PWH using opioids. Increasing autophagic activity in the context of HIV may represent a novel therapeutic strategy for reducing HAND in these individuals. |
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معلومات مُعتمدة: | 5R01DA044584 United States NH NIH HHS; 5T32GM007288-44 United States NH NIH HHS; 2T32AI070117-13 United States NH NIH HHS; 5R01DA048609 United States NH NIH HHS; R01 DA044584 United States DA NIDA NIH HHS; P30 AG038072 United States AG NIA NIH HHS; F30 DA053118 United States DA NIDA NIH HHS; T32 GM007288 United States GM NIGMS NIH HHS; R01 DA048609 United States DA NIDA NIH HHS; P30 AI124414 United States AI NIAID NIH HHS; T32 AI070117 United States AI NIAID NIH HHS |
فهرسة مساهمة: | Keywords: HIV-associated neurocognitive disorders; LC3; antiretroviral therapy; autophagy; mitophagy; myeloid cells; opioids; p62/SQSTM1; selective autophagy |
المشرفين على المادة: | 0 (Anti-Retroviral Agents) 76I7G6D29C (Morphine) |
تواريخ الأحداث: | Date Created: 20210928 Date Completed: 20211119 Latest Revision: 20220518 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC8470112 |
DOI: | 10.3390/cells10092183 |
PMID: | 34571832 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2073-4409 |
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DOI: | 10.3390/cells10092183 |