Neuroprotective Role of Galectin-1 on the Neuropathogenesis of HIV-1

Undergraduate #110
Discipline: Biological Sciences
Subcategory: Microbiology/Immunology/Virology

Courtney S. Mangum - Tougaloo College
Co-Author(s): Jessica L. Reynolds, Stanley A. Schwartz, and Supriya D. Mahajan, State University of New York at Buffalo, Clinical Translational Research Center, Buffalo, NY

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Human immunodeficiency virus (HIV) enters the central nervous system (CNS) early in HIV infection and impacts neuronal cells such as astrocytes, microglia, and neurons, causing mild to moderate neurological deficits. This leads to a disease known as HIV associated neurocognitive disorder (HAND). Nitric oxide (NO) is a cellular signaling molecule that plays an important role in neuroinflammation. iNOS is involved in immune response and produces NO, which is proinflammatory. L-arginine is used as a substrate by both nitric oxide synthase (NOS) and arginase to produce nitric oxide (NO) and urea. NO production may be reduced by arginase via depleting the common substrate Larginine in microglia. Therefore, an increase in arginase activity reduces the available arginine substrate for NO production. Galectin-1, found within astrocytes, is neuroprotective and decreases NO via the increased arginase I expression. This protein will reduce neuroinflammation in the human microglia cell line CHME5 and CHME5-HIV. Treatment of Microglia with proinflammatory cytokines TNF-a/INF-g or LPS treatment, which stimulates proinflammatory cytokines results in increase in oxidative stress as measured by oxygen species (ROS) production. ROS include superoxide (O2), hydrogen peroxide (H2O2) and hydroxyl radical (OH), which under physiological conditions are generated at low levels and play important roles in signaling and metabolic pathways. Increased oxidative stress causes the generation of ROS, which are potentially toxic for cells further contributing to neuroinflammation. Treatment of microglia with pro-inflammatory cytokines TNF-a/INF-g or LPS resulted in 60 % increase (p<0.01) in oxidative stress in CHME-5 and a 26% increase (p<0.05) in CHME5/HIV respectively compared to the untreated control. Treatment of microglia with Galectin-1 (1mM) reduced oxidative stress by ~ 25% (p<0.05) in CHME5 and by ~60% in CHME-5/HIV. With the addition of Galectin-1, NO production was reduced while the arginase activity increase. Galectin-1 shows to reduce neuroinflammation via the modulation of the nitric oxide network and may potentially play a neuroprotective role in HAND.

Funder Acknowledgement(s): Department of Medicine, State University of New York at Buffalo, Clinical Translational Research Center

Faculty Advisor: Supriya Mahajan,