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HIV-1 Tat protein-dependent cytotoxicity is attenated by 15-deoxy-Delta12,14-Prostaglandin J2 in rat hippocampal slices: Involvement of the ERK1/2 signaling pathway

Title
HIV-1 Tat protein-dependent cytotoxicity is attenated by 15-deoxy-Delta12,14-Prostaglandin J2 in rat hippocampal slices: Involvement of the ERK1/2 signaling pathway
Authors
Lee E.O.Yang J.H.Kim J.H.Woo S.Y.Chong Y.H.
Ewha Authors
정영해우소연
SCOPUS Author ID
정영해scopus; 우소연scopus
Issue Date
2013
Journal Title
Journal of Bacteriology and Virology
ISSN
1598-2467JCR Link
Citation
vol. 43, no. 1, pp. 45 - 53
Indexed
SCOPUS; KCI scopus
Abstract
15-deoxy-delta12,14 prostaglandin J2 (15d-PGJ2) may hold promise in treatment of the pathologies associated with human immunodeficiency virus (HIV) infection of the central nervous system. However, its precise role and neuroprotective mechanism in the hippocampus remain poorly understood. In the present study, rat hippocampal slices were stimulated with HIV-1 Tat protein to investigate the protective role of 15d-PGJ2 on the hippocampal cytotoxicity. Full-length HIV-1 Tat protein (Tat1-86), but neither its Tat32-62 nor Tat30-86 fragment, significantly induced cytotoxicity in the hippocampus, the brain region most commonly damaged in HIV-associated dementia. This Tat-induced cytotoxicity was associated with inactivation of MEK/extracellular signal-regulated kinase (ERK) signaling pathway. In contrast, Tat1-86 did not alter Wnt signaling pathway necessary for cell survival. Pretreatment of slices with 15d-PGJ2 markedly reduced Tat-driven cytotxicity. Interestingly, this reduction was accompanied by suppression of ERK inactivation in response to Tat. Moreover, the inhibition of the MEK/ERK pathway with SL327 enhanced the Tat-induced cytotoxicity, confirming the ERK-dependent mechanism of Tat-driven cytotoxicity. Collectively, these data demonstrate that the protective action of 15d-PGJ2 against the hippocampal cytotoxicity upon Tat stimulation is exerted through suppression of Tat-mediated ERK1/2 inactivation.
DOI
10.4167/jbv.2013.43.1.45
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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