HIV-1 gp120 primes lymphocytes for opioid-induced, beta-arrestin 2-dependent apoptosis.

HIV-1 gp120 primes lymphocytes for opioid-induced, beta-arrestin 2-dependent apoptosis.
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DOI:
10.1016/j.bbamcr.2009.05.007
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发表时间:
2009-08
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Yin D
Yin D
中科院分区:
其他
文献类型:
--
作者:
Moorman J;Zhang Y;Liu B;LeSage G;Chen Y;Stuart C;Prayther D;Yin D

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阿片类药物影响人类免疫缺陷病毒1型(HIV-1)感染进展的机制尚未明确。HIV-1 gp 120在未感染的旁观者T细胞的凋亡中是重要的。在这项研究中,我们表明,共同治疗的人外周血单个核细胞(PBMC)与HIV-1 gp 120/吗啡协同诱导PBMC的凋亡。与野生型小鼠的脾细胞相比,用gp 120/吗啡共处理μ阿片受体敲除小鼠的脾细胞导致凋亡减少。用gp 120/吗啡共处理人PBMC或鼠脾细胞导致β-arrestin 2的表达降低,β-arrestin 2是阿片样物质介导的信号传导所需的蛋白质。在Jurkat淋巴细胞中证实了β-arrestin 2的作用:1)过表达β-arrestin 2抑制gp 120/吗啡诱导的细胞凋亡; 2)RNA干扰β-arrestin 2表达增强gp 120/吗啡诱导的细胞凋亡。这些数据表明,HIV-1 gp 120和阿片类药物诱导淋巴细胞死亡的一种新机制。
The mechanisms by which opioids affect progression of human immunodeficiency virus type 1 (HIV-1) infection are not well-defined. HIV-1 gp120 is important in the apoptotic death of uninfected, bystander T cells. In this study, we show that co-treatment of human peripheral blood mononuclear cells (PBMC) with HIV-1 gp120/morphine synergistically induces apoptosis in PBMC. Co-treatment of murine splenocytes from μ opiate receptor knockout mice with gp120/morphine resulted in decreased apoptosis when compared splenocytes from wild type mice. Co-treatment of human PBMC or murine splenocytes with gp120/morphine led to decreased expression of β–arrestin 2, a protein required for opioid-mediated signaling. The role of β–arrestin 2 was confirmed in Jurkat lymphocytes, in which 1) over-expression of β–arrestin 2 inhibited gp120/morphine-induced apoptosis and 2) RNA interference of β–arrestin 2 expression enhanced gp120/morphine-induced apoptosis. These data suggest a novel mechanism by which HIV-1 gp120 and opioids induce lymphocyte cell death.
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