Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant Subline.
Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant Subline.
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Cry41Aa，也被称为parasporin-3，属于一组来自昆虫致病细菌苏云金芽孢杆菌的毒素，对人类癌细胞有活性。Cry41Aa在蛋白水解激活后，对HL-60（人早幼粒细胞白血病细胞）和HepG2（人肝癌细胞）细胞系表现出优先杀伤活性。为了更好地了解Cry41Aa的作用机制，我们在HepG2细胞中通过反复暴露于增加剂量的毒素而进化出耐药性。Cry41Aa杀死50%以上亲本HepG2细胞的浓度对抗性细胞的活力没有显著影响，也没有诱导孔形成或p38磷酸化（这两者都是成孔毒素的特征）。初步的RNA测序数据确定AQP9是潜在的耐药介质，但广泛的研究未能显示因果关系，也不支持增强的细胞修复过程作为耐药机制。
Cry41Aa, also called parasporin-3, belongs to a group of toxins from the entomopathogenic bacterium Bacillus thuringiensis that show activity against human cancer cells. Cry41Aa exhibits preferential cytocidal activity towards HL-60 (human promyelocytic leukaemia cells) and HepG2 (human liver cancer cells) cell lines after being proteolytically activated. To better understand the mechanism of action of Cry41Aa, we evolved resistance in HepG2 cells through repeated exposure to increasing doses of the toxin. Concentrations of Cry41Aa that killed over 50% of the parental HepG2 cells had no significant effect on the viability of the resistant cells and did not induce either pore formation or p38 phosphorylation (both characteristic features of pore-forming toxins). Preliminary RNA sequencing data identified AQP9 as a potential mediator of resistance, but extensive investigations failed to show a causal link and did not support an enhanced cell repair process as the resistance mechanism.
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影响因子：
30.3
作者：
Los FC;Kao CY;Smitham J;McDonald KL;Ha C;Peixoto CA;Aroian RV
通讯作者：
Aroian RV
影响因子：
4.8
作者：
Cai, Beibei;Chang, Sandra H.;Xia, Zhengui
通讯作者：
Xia, Zhengui
影响因子：
4.8
作者：
Ratner, AJ;Hippe, KR;Weiser, JN
通讯作者：
Weiser, JN
影响因子：
4.4
作者：
Gunning, RV;Dang, HT;Moores, GD
通讯作者：
Moores, GD
影响因子：
4.8
作者：
Oppert, B;Kramer, KJ;McGaughey, WH
通讯作者：
McGaughey, WH