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Human immunodeficiency virus type‐1 Tat protein induces nuclear factor (NF)‐κB activation and oxidative stress in microglial cultures by independent mechanisms
Author(s) -
Nicolini Alessia,
AjmoneCat Maria Antonietta,
Bernardo Antonietta,
Levi Giulio,
Minghetti Luisa
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00568.x
Subject(s) - oxidative stress , nitric oxide , cytokine , lipid peroxidation , chemistry , tumor necrosis factor alpha , nf κb , nfkb1 , biochemistry , microbiology and biotechnology , biology , signal transduction , endocrinology , immunology , transcription factor , gene
We have extended our previous findings and shown that human immunodeficiency virus Tat protein, in addition to nitric oxide (NO), stimulated rat microglial cultures to release pro‐inflammatory cytokine interleukin‐1β and tumour necrosis factor‐α in a nuclear factor (NF)‐κB‐dependent manner. At the same time, Tat stimulated the accumulation of free radicals, as indicated by the increased levels of isoprostane 8‐epi‐prostaglandin F 2α (8‐epi‐PGF 2α ), a reliable marker of lipid peroxidation and oxidative stress, by a mechanism unrelated to NF‐κB activation. The presence of free radical scavengers abrogated Tat‐induced 8‐epi‐PGF 2α accumulation without affecting NO and cytokine production. Consistently, Tat‐induced IκBα degradation – an index of NF‐κB activation – was not affected by free radical scavengers, but was prevented by an NF‐κB‐specific inhibitor. Our observations indicate that NF‐κB plays a key role in Tat‐dependent microglial activation, and that oxidative stress and NF‐κB activation induced by Tat occur by independent mechanisms.