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Red Algal Sulfated Galactan Binds and Protects Neural Cells from HIV-1 gp120 and Tat.
Pomin VH
,
Mahdi F
,
Jin W
,
Zhang F
,
Linhardt RJ
,
Paris JJ
.
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The potential neuroprotective capacity of four different sulfated glycans: Botryocladia occidentalis-derived sulfated galactan (BoSG) (MW > 100 kDa), Lytechinus variegatus-derived sulfated fucan (LvSF) (MW~90 kDa), high-molecular weight dextran sulfate (DxS) (MW 100 kDa), and unfractionated heparin (UFH) (MW~15 kDa), was assessed in response to the HIV-1 proteins, R5-tropic glycoprotein 120 (gp120) and/or trans-activator of transcription (Tat), using primary murine neurons co-cultured with mixed glia. Compared to control-treated cells in which HIV-1 proteins alone or combined were neurotoxic, BoSG was, among the four tested sulfated glycans, the only one capable of showing significant concentration-dependent neuroprotection against Tat and/or gp120, alone or combined. Surface plasmon resonance-based data indicate that BoSG can bind both HIV-1 proteins at nM concentrations with preference for Tat (7.5 × 10-8 M) over gp120 (3.2 × 10-7 M) as compared to UFH, which bound gp120 (8.7 × 10-7 M) over Tat (5.7 × 10-6 M). Overall, these data support the notion that sulfated glycan extracted from the red alga B. occidentalis, BoSG, can exert neuroprotection against HIV-1 Tat and gp120, potentially via direct molecular interactions.
Figure 1. Structural representation of unfractionated heparin, UFH (A); dextran sulfate, DxS (B); Lytechinus variegatus sulfated fucan, LvSF (C); and Botryocladia occidentalis sulfated galactan, BoSG (D).
Figure 2. Representative photomicrographs (40×) of C57BL/6N, striatal, medium spiny neurons co-exposed to Botryocladia occidentalis sulfated galactan (BoSG) or unfractionated heparin (UFH) and the HIV proteins, Tat (50 ng/mL) and/or gp120 (500 pM). Total cell number was assessed via Hoechst 33342 (blue) and cell death was confirmed via propidium iodide (red). Arrows indicate examples of propidium-iodide-positive cells. Scale bar = 20 µM.
Figure 3. Neuronal cell death among C57BL/6N, striatal, medium spiny neurons co-exposed to Botryocladia occidentalis sulfated galactan (BoSG; 1, 10, and 100 μg/mL), HIV-1 Tat (50 ng/mL), and/or HIV-1 gp120 (500 pM). * indicates significant increase in necrosis compared to untreated media control. † indicates significant protection from respective HIV-1 protein exposure. All points indicate the mean of 3–5 independent experiments (two-way ANOVA, p ≤ 0.05).
Figure 4. Neuronal cell death among C57BL/6N, striatal, medium spiny neurons co-exposed to Lytechinus variegatus-derived sulfated fucan (LvSF; 1 and 10 μg/mL), high-molecular weight dextran sulfate (DxS; 100 µg/mL), unfractionated heparin (UFH; 100 µg/mL), HIV-1 Tat (50 ng/mL), and/or HIV-1 gp120 (500 pM). * indicates significant increase in necrosis compared to untreated media control. † indicates significant protection from respective HIV-1 protein exposure. All points indicate the mean of 2–5 independent experiments (two-way ANOVA, p ≤ 0.05).
Figure 5. SPR sensorgrams of unfractionated heparin UFH; (A,B) and Botryocladia occidentalis sulfated galactan BoSG; (C,D) in interactions with HIV-1 Tat (A,C) and gp120 (B,D). Concentrations of HIV-1 proteins are shown color-coded in the panels. The black curves are the fitting curves using models from BIAevaluate 4.0.1.
Ajasin,
HIV-1 Tat: Role in Bystander Toxicity.
2020, Pubmed
Ajasin,
HIV-1 Tat: Role in Bystander Toxicity.
2020,
Pubmed
Amornrut,
A new sulfated beta-galactan from clams with anti-HIV activity.
1999,
Pubmed
Argyris,
The perlecan heparan sulfate proteoglycan mediates cellular uptake of HIV-1 Tat through a pathway responsible for biological activity.
2004,
Pubmed
Baroletti,
Heparin-induced thrombocytopenia.
2006,
Pubmed
Caccuri,
HIV-1 Matrix Protein p17 and its Receptors.
2016,
Pubmed
Castro,
A unique 2-sulfated {beta}-galactan from the egg jelly of the sea urchin Glyptocidaris crenularis: conformation flexibility versus induction of the sperm acrosome reaction.
2009,
Pubmed
,
Echinobase
Chang,
HIV-1 Tat protein exits from cells via a leaderless secretory pathway and binds to extracellular matrix-associated heparan sulfate proteoglycans through its basic region.
1997,
Pubmed
Cladera,
The fusion domain of HIV gp41 interacts specifically with heparan sulfate on the T-lymphocyte cell surface.
2001,
Pubmed
Connell,
Human immunodeficiency virus and heparan sulfate: from attachment to entry inhibition.
2013,
Pubmed
Crublet,
The HIV-1 envelope glycoprotein gp120 features four heparan sulfate binding domains, including the co-receptor binding site.
2008,
Pubmed
De Francesco,
HIV-1 p17 matrix protein interacts with heparan sulfate side chain of CD44v3, syndecan-2, and syndecan-4 proteoglycans expressed on human activated CD4+ T cells affecting tumor necrosis factor alpha and interleukin 2 production.
2011,
Pubmed
Farias,
Structure and anticoagulant activity of sulfated galactans. Isolation of a unique sulfated galactan from the red algae Botryocladia occidentalis and comparison of its anticoagulant action with that of sulfated galactans from invertebrates.
2000,
Pubmed
Farias,
A preponderantly 4-sulfated, 3-linked galactan from the green alga Codium isthmocladum.
2008,
Pubmed
Farndale,
Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue.
1986,
Pubmed
Flexner,
Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection.
1991,
Pubmed
Fonseca,
Slight differences in sulfation of algal galactans account for differences in their anticoagulant and venous antithrombotic activities.
2008,
Pubmed
Hileman,
Glycosaminoglycan-protein interactions: definition of consensus sites in glycosaminoglycan binding proteins.
1998,
Pubmed
Huang,
The depolymerized fucosylated chondroitin sulfate from sea cucumber potently inhibits HIV replication via interfering with virus entry.
2013,
Pubmed
,
Echinobase
Kim,
A central role for glial CCR5 in directing the neuropathological interactions of HIV-1 Tat and opiates.
2018,
Pubmed
Langford,
Doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) as an HIV/neuroAIDS model.
2018,
Pubmed
Ma,
The blood-brain barrier accessibility of a heparin-derived oligosaccharides C3.
2002,
Pubmed
Melo,
Antithrombin-mediated anticoagulant activity of sulfated polysaccharides: different mechanisms for heparin and sulfated galactans.
2004,
Pubmed
Mulloy,
Sulfated fucans from echinoderms have a regular tetrasaccharide repeating unit defined by specific patterns of sulfation at the 0-2 and 0-4 positions.
1994,
Pubmed
,
Echinobase
Nickoloff-Bybel,
HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System.
2020,
Pubmed
Paris,
5α-reduced progestogens ameliorate mood-related behavioral pathology, neurotoxicity, and microgliosis associated with exposure to HIV-1 Tat.
2016,
Pubmed
Paris,
Pregnane steroidogenesis is altered by HIV-1 Tat and morphine: Physiological allopregnanolone is protective against neurotoxic and psychomotor effects.
2020,
Pubmed
Poiesi,
HIV-1 p17 binds heparan sulfate proteoglycans to activated CD4(+) T cells.
2008,
Pubmed
Pomin,
Sulfated Glycans in HIV Infection and Therapy.
2017,
Pubmed
Pomin,
Current structural biology of the heparin interactome.
2015,
Pubmed
Pomin,
Fucanomics and galactanomics: current status in drug discovery, mechanisms of action and role of the well-defined structures.
2012,
Pubmed
Pugliese,
A review of cardiovascular complications accompanying AIDS.
2004,
Pubmed
Quinderé,
Is the antithrombotic effect of sulfated galactans independent of serpin?
2014,
Pubmed
Raybuck,
A GluN2B-Selective NMDAR Antagonist Reverses Synapse Loss and Cognitive Impairment Produced by the HIV-1 Protein Tat.
2017,
Pubmed
Richard,
Cellular uptake of unconjugated TAT peptide involves clathrin-dependent endocytosis and heparan sulfate receptors.
2005,
Pubmed
Salahuddin,
Combined HIV-1 Tat and oxycodone activate the hypothalamic-pituitary-adrenal and -gonadal axes and promote psychomotor, affective, and cognitive dysfunction in female mice.
2020,
Pubmed
Schier,
Selective Vulnerability of Striatal D2 versus D1 Dopamine Receptor-Expressing Medium Spiny Neurons in HIV-1 Tat Transgenic Male Mice.
2017,
Pubmed
Speidell,
Up-regulation of the p75 neurotrophin receptor is an essential mechanism for HIV-gp120 mediated synaptic loss in the striatum.
2020,
Pubmed
Tazi,
Determination of residual dextran sulfate in protein products by SEC-HPLC.
2016,
Pubmed
Thaney,
Type I Interferons in NeuroHIV.
2019,
Pubmed
Thaney,
Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research.
2018,
Pubmed
Tyagi,
Internalization of HIV-1 tat requires cell surface heparan sulfate proteoglycans.
2001,
Pubmed
Urbinati,
HIV-1 Tat and heparan sulfate proteoglycan interaction: a novel mechanism of lymphocyte adhesion and migration across the endothelium.
2009,
Pubmed
Vivès,
Heparan sulfate targets the HIV-1 envelope glycoprotein gp120 coreceptor binding site.
2005,
Pubmed
Ziegler,
Interaction of the protein transduction domain of HIV-1 TAT with heparan sulfate: binding mechanism and thermodynamic parameters.
2004,
Pubmed
Zoepfl,
Antiviral activities of four marine sulfated glycans against adenovirus and human cytomegalovirus.
2021,
Pubmed
,
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