Prolonged cigarette smoke exposure decreases heme oxygenase-1 and alters Nrf2 and Bach1 expression in human macrophages: Roles of the MAP kinases ERK1/2 and JNK

Prolonged cigarette smoke exposure decreases heme oxygenase-1 and alters Nrf2 and Bach1 expression in human macrophages: Roles of the MAP kinases ERK1/2 and JNK
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DOI:
10.1016/j.febslet.2009.10.010
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发表时间:
2009-11-03
期刊:
影响因子:
3.5
通讯作者:
Bonay, M.
Bonay, M.
中科院分区:
生物学3区
文献类型:
--
作者:
Goven, D.;Boutten, A.;Bonay, M.

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烟草可能通过核因子红细胞 2 相关因子 2 (Nrf2)/Kelch 样 ECH 相关蛋白 1 (Keap1)-BTB 和 CNC 同源性 1、碱性亮氨酸拉链转录因子 1 (Bach1) 途径参与吸烟引起的严重肺气肿中巨噬细胞血红素加氧酶 - 1 (HO-1) 表达的减少。我们评估了香烟烟雾冷凝物 (CS) 对人单核细胞/巨噬细胞系 (THP-1) 的体外影响。 CS暴露导致HO-1和核Nrf2表达增加(6小时),随后HO-1表达减少,同时核Nrf2/Bach1比率降低(72小时)。 CS 诱导丝裂原激活蛋白激酶 (MAPK) 磷酸化。细胞外信号调节激酶1/2 (ERK1/2) 和c-Jun NH2 末端激酶(JNK) 抑制完全消除了CS 对HO-1 表达和核Nrf2/Bach1 易位的影响。这些结果表明 ERK1/2 和 JNK 通过 Nrf2/Keap1-Bach1 的特异性调节参与 CS 诱导的双相 HO-1 表达。 (C) 2009 年欧洲生化学会联合会。由 Elsevier B.V 出版。保留所有权利。
Tobacco may be involved in the decreased macrophage heme oxygenase-1 (HO-1) expression described in smoking-induced severe emphysema, via the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-BTB and CNC homology 1, basic leucine zipper transcription factor 1 (Bach1) pathway. We assessed in vitro effects of cigarette smoke condensate (CS) in the human monocyte/macrophage cell line (THP-1). CS exposure led to increased HO-1 and nuclear Nrf2 expression (6 h) followed by decreased HO-1 expression concomitantly with nuclear Nrf2/Bach1 ratio decrease (72 h). CS-induced mitogen-activated protein kinase (MAPK) phosphorylation. Extracellular-signal-regulated kinase1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK) inhibition completely abrogated CS effects on HO-1 expression and nuclear Nrf2/Bach1 translocation. These results suggest that ERK1/2 and JNK are involved in CS-induced biphasic HO-1 expression by a specific regulation of Nrf2/Keap1-Bach1. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.