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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
- 정영해; 우소연
- SCOPUS Author ID
- 정영해; 우소연
- Issue Date
- 2013
- Journal Title
- Journal of Bacteriology and Virology
- ISSN
- 1598-2467
- Citation
- Journal of Bacteriology and Virology vol. 43, no. 1, pp. 45 - 53
- Indexed
- SCOPUS; KCI
- Document Type
- Article
- 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:
- 의과대학 > 의학과 > Journal papers
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