title: Human immunodeficiency virus type 1 clade B and C gp120 differentially induce neurotoxin arachidonic acid in human astrocytes: implications for neuroAIDS.
abstract: HIV-1 clades (subtypes) differentially contribute to the neuropathogenesis of HIV-associated dementia (HAD) in neuroAIDS. HIV-1 envelop protein, gp120, plays a major role in neuronal function. It is not well understood how these HIV-1 clades exert these neuropathogenic differences. The N-methyl-D: -aspartate (NMDA) receptor-reduced glutamine synthesis could lead to secretion of neurotoxins such as arachidonic acid (AA) which plays a significant role in the neuropathogenic mechanisms in neuroAIDS. We hypothesize that clade B and C gp120 proteins exert differential effects on human primary astrocytes by production of the neurotoxin arachidonic acid. Our results indicate that clade B gp120 significantly downregulated NMDA receptor gene and protein expression, and level of glutamine while increasing expression of prostaglandin E2 (PGE(2)) and thromboxane A2 receptor (TBXA(2) R) compared to HIV-1 clade C gp120 protein. Thus, our studies for the first time demonstrate that HIV-1 clade B-gp120 protein appears to induce higher levels of expression of the neuropathogenic molecule cyclooxygenase-2 (COX-2)-mediated arachidonic acid by-products, PGE(2), and TBXA(2) R compared to HIV-1 clade C gp120 protein. These studies suggest that HIV-1 clade B and C gp120 proteins may play a differential role in the neuropathogenesis of HAD in neuroAIDS.
authors.affiliation: Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, 11200 S.W. 8th Street, HLS-1 #418A, Miami, FL 33199, USA.
authors.forename: Thangavel
authors.initials: T
authors.lastname: Samikkannu
authors.forename: Marisela
authors.initials: M
authors.lastname: Agudelo
authors.forename: Nimisha
authors.initials: N
authors.lastname: Gandhi
authors.forename: Pichili V B
authors.initials: PV
authors.lastname: Reddy
authors.forename: Zainulabedin M
authors.initials: ZM
authors.lastname: Saiyed
authors.forename: Donald
authors.initials: D
authors.lastname: Nwankwo
authors.forename: Madhavan P N
authors.initials: MP
authors.lastname: Nair
mesh_terms: D015526:AIDS Dementia Complex / Q000378:metabolism* / Q000473:pathology; D016718:Arachidonic Acid / Q000096:biosynthesis*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation; D005973:Glutamine / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000494:pharmacology*; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D009498:Neurotoxins / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000378:metabolism / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D015699:HIV Envelope Protein gp120; D009498:Neurotoxins; D020033:Protein Isoforms; D016194:Receptors, N-Methyl-D-Aspartate; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D005973:Glutamine; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone