Circulating levels of ATP is a biomarker of HIV cognitive impairment.
Title | Circulating levels of ATP is a biomarker of HIV cognitive impairment. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Velasquez, S, Prevedel, L, Valdebenito, S, Gorska, AMaria, Golovko, M, Khan, N, Geiger, J, Eugenin, EA |
Journal | EBioMedicine |
Volume | 51 |
Pagination | 102503 |
Date Published | 2020 Jan |
ISSN | 2352-3964 |
Keywords | Adenosine Triphosphate, Adult, Aged, Biomarkers, Blood-Brain Barrier, Cognitive Dysfunction, Connexins, Dinoprostone, External, Female, HIV Infections, Humans, Inflammation Mediators, Ion Channel Gating, Leukocytes, Mononuclear, Male, Middle Aged, Nerve Tissue Proteins, Transendothelial and Transepithelial Migration |
Abstract | 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 PGE and ATP. Also, we correlated the opening of Panx-1 channels with the circulating levels of PGE 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 PGE 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 PGE 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. |
DOI | 10.1016/j.ebiom.2019.10.029 |
Alternate Journal | EBioMedicine |
PubMed ID | 31806564 |
PubMed Central ID | PMC7000317 |
Grant List | U24 MH100929 / MH / NIMH NIH HHS / United States U24 MH100925 / MH / NIMH NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States U54 GM115458 / GM / NIGMS NIH HHS / United States R01 MH096625 / MH / NIMH NIH HHS / United States R25 MH080663 / MH / NIMH NIH HHS / United States R01 MH119000 / MH / NIMH NIH HHS / United States R01 NS105584 / NS / NINDS NIH HHS / United States R01 MH100972 / MH / NIMH NIH HHS / United States R01 DA032444 / DA / NIDA NIH HHS / United States R01 GM100329 / GM / NIGMS NIH HHS / United States R01 NS065957 / NS / NINDS NIH HHS / United States U24 MH100931 / MH / NIMH NIH HHS / United States R01 MH105329 / MH / NIMH NIH HHS / United States U24 MH100930 / MH / NIMH NIH HHS / United States |