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Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome drug candidate, decreased vulnerability of PC12 cells to human immunodeficiency virus tat protein through attenuating calcium overload.
J Neurosci Res. 2008 Apr; 86(5):1169-77.JN

Abstract

Human immunodeficiency virus (HIV)-1 infection of the central nervous system occurs in the vast majority of HIV-infected patients. HIV-associated dementia (HAD) represents the most severe form of HIV-related neuropsychiatric impairment. The pathogenesis of HAD is mediated by disruption of neuronal cell signal pathways, which ultimately triggers neuronal apoptosis. Evidence indicates that a viral gene product, the transactivator of transcription protein (Tat), takes a responsive role to these events. We herein report that sulfated polymannuroguluronate (SPMG), a novel anti-acquired immunodeficiency syndrome drug candidate now in phase II clinical trial, significantly decreased vulnerability of PC12 cells to HIV Tat protein by protecting cells from apoptosis. Furthermore, SPMG potently arrested Tat-triggered PKCdelta and PKCtheta activation and blocked the downstream apoptosis signaling pathways mediated by both ERK1/2 and caspase-3. These molecular mechanisms were attributed to the fact that SPMG reduced Tat-evoked calcium overload. These data demonstrate that SPMG might serve as a valuable therapeutic intervention for Tat-induced neuronal cell death and the subsequent pathologic events of HAD.

Authors+Show Affiliations

Department of Pharmacology, Marine Drug and Food Institute, Ocean University of China, Qingdao, China.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18092356

Citation

Hui, Bin, et al. "Sulfated Polymannuroguluronate, a Novel Anti-acquired Immune Deficiency Syndrome Drug Candidate, Decreased Vulnerability of PC12 Cells to Human Immunodeficiency Virus Tat Protein Through Attenuating Calcium Overload." Journal of Neuroscience Research, vol. 86, no. 5, 2008, pp. 1169-77.
Hui B, Li J, Geng MY. Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome drug candidate, decreased vulnerability of PC12 cells to human immunodeficiency virus tat protein through attenuating calcium overload. J Neurosci Res. 2008;86(5):1169-77.
Hui, B., Li, J., & Geng, M. Y. (2008). Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome drug candidate, decreased vulnerability of PC12 cells to human immunodeficiency virus tat protein through attenuating calcium overload. Journal of Neuroscience Research, 86(5), 1169-77.
Hui B, Li J, Geng MY. Sulfated Polymannuroguluronate, a Novel Anti-acquired Immune Deficiency Syndrome Drug Candidate, Decreased Vulnerability of PC12 Cells to Human Immunodeficiency Virus Tat Protein Through Attenuating Calcium Overload. J Neurosci Res. 2008;86(5):1169-77. PubMed PMID: 18092356.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome drug candidate, decreased vulnerability of PC12 cells to human immunodeficiency virus tat protein through attenuating calcium overload. AU - Hui,Bin, AU - Li,Jing, AU - Geng,Mei Yu, PY - 2007/12/20/pubmed PY - 2008/4/24/medline PY - 2007/12/20/entrez SP - 1169 EP - 77 JF - Journal of neuroscience research JO - J Neurosci Res VL - 86 IS - 5 N2 - Human immunodeficiency virus (HIV)-1 infection of the central nervous system occurs in the vast majority of HIV-infected patients. HIV-associated dementia (HAD) represents the most severe form of HIV-related neuropsychiatric impairment. The pathogenesis of HAD is mediated by disruption of neuronal cell signal pathways, which ultimately triggers neuronal apoptosis. Evidence indicates that a viral gene product, the transactivator of transcription protein (Tat), takes a responsive role to these events. We herein report that sulfated polymannuroguluronate (SPMG), a novel anti-acquired immunodeficiency syndrome drug candidate now in phase II clinical trial, significantly decreased vulnerability of PC12 cells to HIV Tat protein by protecting cells from apoptosis. Furthermore, SPMG potently arrested Tat-triggered PKCdelta and PKCtheta activation and blocked the downstream apoptosis signaling pathways mediated by both ERK1/2 and caspase-3. These molecular mechanisms were attributed to the fact that SPMG reduced Tat-evoked calcium overload. These data demonstrate that SPMG might serve as a valuable therapeutic intervention for Tat-induced neuronal cell death and the subsequent pathologic events of HAD. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/18092356/Sulfated_polymannuroguluronate_a_novel_anti_acquired_immune_deficiency_syndrome_drug_candidate_decreased_vulnerability_of_PC12_cells_to_human_immunodeficiency_virus_tat_protein_through_attenuating_calcium_overload_ L2 - https://doi.org/10.1002/jnr.21566 DB - PRIME DP - Unbound Medicine ER -