Suppression of autophagy enhances the cytotoxicity of the DNA-damaging aromatic amine p-anilinoaniline.
Suppression of autophagy enhances the cytotoxicity of the DNA-damaging aromatic amine p-anilinoaniline.
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DOI：
10.1016/j.taap.2008.06.017
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发表时间：
2008-10-15
影响因子：
3.8
通讯作者：
Reiners, John J., Jr.
中科院分区：
文献类型：
--
作者：
Elliott, Althea;Reiners, John J., Jr.
p-Anilinoaniline (pAA) is an aromatic amine that is widely used in hair dying applications. It is also a metabolite of metanil yellow, an azo dye that is commonly used as a food coloring agent. Concentrations of pAA between 10–25 μM were cytostatic to cultures of the normal human mammary epithelia cell line MCF10A. Concentrations ≥ 50 μM were cytotoxic. Cytostatic concentrations induced transient G1 and S cell cycle phase arrests; whereas cytotoxic concentrations induced protracted arrests. Cytotoxic concentrations of pAA caused DNA damage, as monitored by the alkaline single-cell gel electrophoresis (Comet) assay, and morphological changes consistent with cells undergoing apoptosis and/or autophagy. Enzymatic and western blot analyses, and binding analyses of fluorescent labeled VAD-FMK, suggested that caspase family members were activated by pAA. Western blot analyses documented the conversion of LC3-I to LC3-II, a post-translational modification involved in the development of the autophagosome. Suppression of autophagosome formation, via knockdown of ATG7 with shRNA, prevented pAA-induced vacuolization, enhanced the activation of pro-caspase-3, and increased susceptibility of ATG7-deficient cells to the cytostatic and cytotoxic activities of markedly lower concentrations of pAA. Cells stably transfected with a nonsense shRNA behaved like parental MCF10A cells. Collectively, these data suggest that MCF10A cultures undergo autophagy as a pro-survival response to concentrations of pAA sufficient to induce DNA damage.
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影响因子：
3.6
作者：
Joiakim, A;Mathieu, PA;Reiners, JJ
通讯作者：
Reiners, JJ
影响因子：
11.2
作者：
Apel, Anja;Herr, Ingrid;Mayer, Andreas
通讯作者：
Mayer, Andreas
影响因子：
12.4
作者：
Katayama, M.;Kawaguchi, T.;Pieper, R. O.
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影响因子：
2.7
作者：
Amstad, PA;Yu, G;Phelps, DJ
通讯作者：
Phelps, DJ
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T