Circulating levels of ATP is a biomarker of HIV cognitive impairment
Background: In developed countries, Human Immunodeficiency Virus type-1 (HIV-1) infection has become a chronic disease despite the positive effects of anti-retroviral therapies (ART), but still at least half of the HIV infected population shown signs of cognitive impairment. Therefore, biomarkers of...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419306929 |
| _version_ | 1818576966460112896 |
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| author | Stephani Velasquez Lisa Prevedel Silvana Valdebenito Anna Maria Gorska Mikhail Golovko Nabab Khan Jonathan Geiger Eliseo A. Eugenin |
| author_facet | Stephani Velasquez Lisa Prevedel Silvana Valdebenito Anna Maria Gorska Mikhail Golovko Nabab Khan Jonathan Geiger Eliseo A. Eugenin |
| author_sort | Stephani Velasquez |
| collection | DOAJ |
| description | Background: In developed countries, Human Immunodeficiency Virus type-1 (HIV-1) infection has become a chronic disease despite the positive effects of anti-retroviral therapies (ART), but still at least half of the HIV infected population shown signs of cognitive impairment. Therefore, biomarkers of HIV cognitive decline are urgently needed. Methods: We analyze the opening of one of the larger channels expressed by humans, pannexin-1 (Panx-1) channels, in the uninfected and HIV infected population (n = 175). We determined channel opening and secretion of intracellular second messengers released through the channel such as PGE2 and ATP. Also, we correlated the opening of Panx-1 channels with the circulating levels of PGE2 and ATP as well as cogntive status of the individuals analyzed. Findings: Here, we demonstrate that Panx-1 channels on fresh PBMCs obtained from uninfected individuals are closed and no significant amounts of PGE2 and ATP are detected in the circulation. In contrast, in all HIV-infected individuals analyzed, even the ones under effective ART, a spontaneous opening of Panx-1 channels and increased circulating levels of PGE2 and ATP were detected. Circulating levels of ATP were correlated with cognitive decline in the HIV-infected population supporting that ATP is a biomarker of cognitive disease in the HIV-infected population. Interpretation: We propose that circulating levels of ATP could predict CNS compromise and lead to the breakthroughs necessary to detect and prevent brain compromise in the HIV-infected population. Keywords: Anti-retroviral/dementia/HIV-1 reservoirs/NeuroHIV/Pannexin |
| first_indexed | 2024-12-16T06:22:25Z |
| format | Article |
| id | doaj.art-d81ec7d2555446a8b2025cd167bde196 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-16T06:22:25Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-d81ec7d2555446a8b2025cd167bde1962022-12-21T22:41:05ZengElsevierEBioMedicine2352-39642020-01-0151Circulating levels of ATP is a biomarker of HIV cognitive impairmentStephani Velasquez0Lisa Prevedel1Silvana Valdebenito2Anna Maria Gorska3Mikhail Golovko4Nabab Khan5Jonathan Geiger6Eliseo A. Eugenin7Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Research Building 17, Fifth Floor, 105 11th Street, Galveston, Texas, 77555, USADepartment of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Research Building 17, Fifth Floor, 105 11th Street, Galveston, Texas, 77555, USADepartment of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Research Building 17, Fifth Floor, 105 11th Street, Galveston, Texas, 77555, USADepartment of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Research Building 17, Fifth Floor, 105 11th Street, Galveston, Texas, 77555, USADepartment of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, USADepartment of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, USADepartment of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, USADepartment of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Research Building 17, Fifth Floor, 105 11th Street, Galveston, Texas, 77555, USA; Corresponding author.Background: In developed countries, Human Immunodeficiency Virus type-1 (HIV-1) infection has become a chronic disease despite the positive effects of anti-retroviral therapies (ART), but still at least half of the HIV infected population shown signs of cognitive impairment. Therefore, biomarkers of HIV cognitive decline are urgently needed. Methods: We analyze the opening of one of the larger channels expressed by humans, pannexin-1 (Panx-1) channels, in the uninfected and HIV infected population (n = 175). We determined channel opening and secretion of intracellular second messengers released through the channel such as PGE2 and ATP. Also, we correlated the opening of Panx-1 channels with the circulating levels of PGE2 and ATP as well as cogntive status of the individuals analyzed. Findings: Here, we demonstrate that Panx-1 channels on fresh PBMCs obtained from uninfected individuals are closed and no significant amounts of PGE2 and ATP are detected in the circulation. In contrast, in all HIV-infected individuals analyzed, even the ones under effective ART, a spontaneous opening of Panx-1 channels and increased circulating levels of PGE2 and ATP were detected. Circulating levels of ATP were correlated with cognitive decline in the HIV-infected population supporting that ATP is a biomarker of cognitive disease in the HIV-infected population. Interpretation: We propose that circulating levels of ATP could predict CNS compromise and lead to the breakthroughs necessary to detect and prevent brain compromise in the HIV-infected population. Keywords: Anti-retroviral/dementia/HIV-1 reservoirs/NeuroHIV/Pannexinhttp://www.sciencedirect.com/science/article/pii/S2352396419306929 |
| spellingShingle | Stephani Velasquez Lisa Prevedel Silvana Valdebenito Anna Maria Gorska Mikhail Golovko Nabab Khan Jonathan Geiger Eliseo A. Eugenin Circulating levels of ATP is a biomarker of HIV cognitive impairment EBioMedicine |
| title | Circulating levels of ATP is a biomarker of HIV cognitive impairment |
| title_full | Circulating levels of ATP is a biomarker of HIV cognitive impairment |
| title_fullStr | Circulating levels of ATP is a biomarker of HIV cognitive impairment |
| title_full_unstemmed | Circulating levels of ATP is a biomarker of HIV cognitive impairment |
| title_short | Circulating levels of ATP is a biomarker of HIV cognitive impairment |
| title_sort | circulating levels of atp is a biomarker of hiv cognitive impairment |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419306929 |
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