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Iron chelation decreases human immunodeficiency virus-1 Tat potentiated tumor necrosis factor-induced NF-kappa B activation in Jurkat cells.
Eur Cytokine Netw 1997; 8(1):37-43EC

Abstract

TNF-alpha stimulates HIV-1 replication via activation of the transcription factor NF-kappa B. TNF-mediated activation of NF-kappa B is known to involve the intracellular formation of reactive oxygen intermediates (ROIs). We recently demonstrated that HIV-1 Tat protein potentiates TNF-induced NF-kappa B activation by downregulation of manganese-dependent superoxide dismutase (MnSOD), shifting the cellular redox state towards pro-oxidative conditions. This study shows that treatment of Jurkat cells with iron chelator deferoxamine (DFO) strongly decreases HIV-1 Tat-potentiated TNF-induced NF-kappa B activation but does not modify NF-kappa B activation by TNF-alpha. The ability of iron chelators to reduce Tat-potentiated TNF-induced NF-kappa B binding activity suggests that iron and intracellular hydroxyl radicals (OH.) are required for Tat effect. Moreover, we have shown that exogenously generated OH. markedly enhanced TNF-induced NF-kappa B activation in a dose-dependent manner while was not sufficient to trigger activation of NF-kappa B by itself. In addition, iron chelators had no effect either on MnSOD activity or on the decrease of this activity by Tat. Iron chelators had also no effect on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), but could elevate the GSH:GSSG ratio decreased by Tat protein. These observations suggest that the formation of intracellular OH. in the presence of iron ions play a major role in HIV-1 Tat enhancement of TNF-induced NF-kappa B activation and that iron chelation may protect Jurkat T cells, at least in part, against oxidative stress induced by Tat.

Authors+Show Affiliations

CJF 94-11 INSERM Cytokines et Immunité Antitumorale, Institut Gustave-Roussy, Villejuif, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9110146

Citation

Shatrov, V A., et al. "Iron Chelation Decreases Human Immunodeficiency Virus-1 Tat Potentiated Tumor Necrosis Factor-induced NF-kappa B Activation in Jurkat Cells." European Cytokine Network, vol. 8, no. 1, 1997, pp. 37-43.
Shatrov VA, Boelaert JR, Chouaib S, et al. Iron chelation decreases human immunodeficiency virus-1 Tat potentiated tumor necrosis factor-induced NF-kappa B activation in Jurkat cells. Eur Cytokine Netw. 1997;8(1):37-43.
Shatrov, V. A., Boelaert, J. R., Chouaib, S., Dröge, W., & Lehmann, V. (1997). Iron chelation decreases human immunodeficiency virus-1 Tat potentiated tumor necrosis factor-induced NF-kappa B activation in Jurkat cells. European Cytokine Network, 8(1), pp. 37-43.
Shatrov VA, et al. Iron Chelation Decreases Human Immunodeficiency Virus-1 Tat Potentiated Tumor Necrosis Factor-induced NF-kappa B Activation in Jurkat Cells. Eur Cytokine Netw. 1997;8(1):37-43. PubMed PMID: 9110146.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iron chelation decreases human immunodeficiency virus-1 Tat potentiated tumor necrosis factor-induced NF-kappa B activation in Jurkat cells. AU - Shatrov,V A, AU - Boelaert,J R, AU - Chouaib,S, AU - Dröge,W, AU - Lehmann,V, PY - 1997/3/1/pubmed PY - 1997/3/1/medline PY - 1997/3/1/entrez SP - 37 EP - 43 JF - European cytokine network JO - Eur. Cytokine Netw. VL - 8 IS - 1 N2 - TNF-alpha stimulates HIV-1 replication via activation of the transcription factor NF-kappa B. TNF-mediated activation of NF-kappa B is known to involve the intracellular formation of reactive oxygen intermediates (ROIs). We recently demonstrated that HIV-1 Tat protein potentiates TNF-induced NF-kappa B activation by downregulation of manganese-dependent superoxide dismutase (MnSOD), shifting the cellular redox state towards pro-oxidative conditions. This study shows that treatment of Jurkat cells with iron chelator deferoxamine (DFO) strongly decreases HIV-1 Tat-potentiated TNF-induced NF-kappa B activation but does not modify NF-kappa B activation by TNF-alpha. The ability of iron chelators to reduce Tat-potentiated TNF-induced NF-kappa B binding activity suggests that iron and intracellular hydroxyl radicals (OH.) are required for Tat effect. Moreover, we have shown that exogenously generated OH. markedly enhanced TNF-induced NF-kappa B activation in a dose-dependent manner while was not sufficient to trigger activation of NF-kappa B by itself. In addition, iron chelators had no effect either on MnSOD activity or on the decrease of this activity by Tat. Iron chelators had also no effect on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), but could elevate the GSH:GSSG ratio decreased by Tat protein. These observations suggest that the formation of intracellular OH. in the presence of iron ions play a major role in HIV-1 Tat enhancement of TNF-induced NF-kappa B activation and that iron chelation may protect Jurkat T cells, at least in part, against oxidative stress induced by Tat. SN - 1148-5493 UR - https://www.unboundmedicine.com/medline/citation/9110146/Iron_chelation_decreases_human_immunodeficiency_virus_1_Tat_potentiated_tumor_necrosis_factor_induced_NF_kappa_B_activation_in_Jurkat_cells_ DB - PRIME DP - Unbound Medicine ER -