Regulation of topoisomerase II α and β in HIV-1 infected and uninfected neuroblastoma and astrocytoma cells: Involvement of distinct nordihydroguaretic acid sensitive inflammatory pathways

Abstract

The activity of Topoisomerase II α and β isoforms is tightly regulated during different phases of cell cycle. In the present study, the action of anti-inflammatory agents, nordihydroguaretic acid (NDGA) is analyzed in HIV-1 infected CXCR4+, CCR5+ and CD4- SK-N-SH neuroblastoma, CXCR4+, CCR5+ and CD4- 1321N1 astrocytoma and CXCR4+, CCR5+/- and CD4- GO-G-CCM glioblastoma cell lines. In SK-N-SH and 1321N1 the expression of Topoisomerase II α is concomitant with that of LOX-5 and is highly sensitive to NDGA, while the Topoisomerase II β is expressed along with TNFα and exhibits low sensitivity to NDGA, suggesting distinct pathways of regulation for the two isoforms. HIV-1 infection in these cells enhanced the expression of Topo II α and β. Further, the regulation of Topo II β and TNFα in infected and uninfected SK cells is distinctly different. HIV-1 gp120 derived peptides could block HIV-1 mediated inflammation and Topoisomerase II α and β expression, suggesting the viral mediated response. A combination of NDGA, gp-120 derived peptides and AZT has completely blocked the viral replication, suggesting the enhancement of potency of AZT under the suppression of inflammatory response. In contrast, the expression of Topo II α and β was stimulated by NDGA in GO-G-CCM cells showing distinct regulatory pathway in these cells that was resistant to HIV-1 infection. This suggests the requirement of inflammatory response for productive viral infection. In summary, an induction of co-receptor mediated inflammatory response can distinctly enhance regulated expression of the cellular Topo II α and β and promote productive infection in neurons and astrocytes. © 2007 Elsevier Inc. All rights reserved.