Perez Omar D, Nolan Garry P, Magda Darren, Miller Richard A, Herzenberg Leonard A, Herzenberg Leonore A
Department of Microbiology and Immunology, The Baxter Laboratories of Genetic Pharmacology, Stanford University, Stanford, CA 94305-5175, USA.
Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2270-4. doi: 10.1073/pnas.261711499.
Here, we show that motexafin gadolinium (Gd-Tex), a compound that promotes intracellular oxidative stress, selectively induces apoptosis in HIV-1-infected CD4(+) T cells in IL-2-stimulated cultures of peripheral blood mononuclear cells infected in vitro with HIV-1. This selective induction of apoptosis, which we detect by FACS analysis of intracellular HIV/p24 and concomitant surface and apoptosis marker expression, is abrogated by the glutathione precursor, N-acetyl-l-cysteine. Importantly, it occurs at Gd-Tex concentrations that are not cytotoxic to uninfected cells in the culture. These findings suggest that Gd-Tex may have therapeutic utility as an anti-HIV agent capable of selectively targeting and removing HIV-infected cells in an infected host.
在此,我们表明莫特沙芬钆(Gd-Tex)是一种可促进细胞内氧化应激的化合物,在体外感染HIV-1的外周血单个核细胞经白细胞介素-2刺激的培养物中,它能选择性地诱导HIV-1感染的CD4(+) T细胞凋亡。我们通过对细胞内HIV/p24进行流式细胞术分析以及同时检测表面和凋亡标志物的表达来检测这种凋亡的选择性诱导,而谷胱甘肽前体N-乙酰-L-半胱氨酸可消除这种诱导作用。重要的是,它在对培养物中未感染细胞无细胞毒性的Gd-Tex浓度下发生。这些发现表明,Gd-Tex作为一种抗HIV药物,可能具有治疗效用,能够在受感染宿主中选择性地靶向并清除HIV感染的细胞。