Microwave & magnetic proteomics of macrophages from patients with HIV-associated cognitive impairment

• Published in: PloS one Vol. 12; no. 7; p. e0181779
• Main Authors: Cantres-Rosario, Yisel M, Acevedo-Mariani, Frances M, Pérez-Laspiur, Juliana, Haskins, William E, Plaud, Marines, Cantres-Rosario, Yadira M, Skolasky, Richard, Méndez-Bermúdez, Israel, Wojna, Valerie, Meléndez, Loyda M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.07.2017; Public Library of Science (PLoS)
• Subjects: Abundance; Analysis of Variance; Antiretroviral agents; Biology and Life Sciences; Blood; Blood-brain barrier; Blotting, Western; Bone surgery; Brain; Brain research; Cells, Cultured; Central nervous system; Chromatography; Chromatography, Liquid; Cognition; Cognition & reasoning; Cognition Disorders - complications; Cognition Disorders - metabolism; Cognitive ability; Cohort Studies; Cross-Sectional Studies; Dehydrogenase; Dementia; Dosage and administration; Enzymes; Female; Gene expression; Glucose; Glucose metabolism; Heat shock proteins; HIV; HIV Infections - complications; HIV Infections - metabolism; Human immunodeficiency virus; Humans; Impairment; Infections; Kinases; Liquid chromatography; Lysates; Macrophages; Macrophages - metabolism; Magnetics; Mass spectrometry; Mass spectroscopy; Medical research; Medicine and Health Sciences; Metabolism; Microwaves; Mitochondrial DNA; Monocytes; Nervous system; Neurotoxicity; Neurotoxins; Oxidative stress; Patient outcomes; Patients; Peptides; Peripheral blood; Protein Interaction Maps; Proteins; Proteome - analysis; Proteome - metabolism; Proteomics; Proteomics - instrumentation; Proteomics - methods; Sample preparation; Scientific imaging; Statistical analysis; Studies; Tandem Mass Spectrometry; Therapy; Toxins; Variance analysis; Zoology; United States > US; Puerto Rico
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0181779

HIV-infected monocytes can infiltrate the blood brain barrier as differentiated macrophages to the central nervous system, becoming the primary source of viral and cellular neurotoxins. The final outcome is HIV-associated cognitive impairment (HACI), which remain prevalent today, possibly due to the longer life-span of the patients treated with combined anti-retroviral therapy. Our main goal was to characterize the proteome of monocyte-derived macrophages (MDM) from HACI patients, and its association with their cognitive status, to find novel targets for therapy. MDM were isolated from the peripheral blood of 14 HIV-seropositive women characterized for neurocognitive function, including: four normal cognition (NC), five asymptomatic (A), and five with cognitive impaired (CI). Proteins from macrophage lysates were isobaric-labeled with the microwave and magnetic (M2) sample preparation method followed by liquid chromatography-tandem mass spectrometry-based protein identification and quantification. Differences in protein abundance across groups classified by HACI status were determined using analysis of variance. A total of 2,519 proteins were identified with 2 or more peptides and 28 proteins were quantified as differentially expressed. Statistical analysis revealed increased abundance of 17 proteins in patients with HACI (p<0.05), including several enzymes associated to the glucose metabolism. Western blot confirmed increased expression of 6-Phosphogluconate dehydrogenase and L-Plastin in A and CI patients over NC and HIV seronegatives. This is the first quantitative proteomics study exploring the changes in protein abundance of macrophages isolated from patients with HACI. Further studies are warranted to determine if these proteins may be target candidates for therapy development against HACI.