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Effect of deoxynivalenol on apoptosis, barrier function, and expression levels of genes involved in nutrient transport, mitochondrial biogenesis and function in IPEC-J2 cells
Toxicology Research ( IF 2.2 ) Pub Date : 2017-08-15 00:00:00 , DOI: 10.1039/c7tx00202e
Peng Liao 1, 2, 3, 4, 5 , Meifang Liao 5, 6, 7, 8 , Ling Li 5, 6, 7, 8 , Bie Tan 1, 2, 3, 4, 5 , Yulong Yin 1, 2, 3, 4, 5
Affiliation  

This study was conducted to determine the effect of 200 ng mL−1 and 2000 ng mL−1 deoxynivalenol (DON) on apoptosis, barrier function, nutrient transporter gene expression, and free amino acid variation as well as on mitochondrial biogenesis and function-related gene expression in the intestinal porcine epithelial cell line J2 (IPEC-J2) for 6 h, 12 h, and 24 h. Exposure to 200 ng mL−1 DON inhibited the cell viability and promoted cell cycle progression from the G2/M phase to the S phase (P < 0.05). The data showed that the IPEC-J2 cell content of free amino acids, such as valine, methionine, leucine, and phenylalanine, was increased (P < 0.05) after treatment for 6 h; the aspartate, threonine, and lysine contents increased (P < 0.05) after treatment for 12 h; and the aspartate, serine, glycine, alanine, isoleucine, leucine, and lysine contents decreased (P < 0.05) after treatment for 24 h. The expression levels of barrier function genes, including zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 1 (CLDN1), showed a significant reduction (P < 0.05). Moreover, the expression levels of differently regulated nutrient transporter genes, including B0,+ amino acid transporter (B0,+AT) and sodium-glucose transporter 1 (SGLT1) genes, showed a significant decrease (P < 0.05), while the Na+-dependent neutral amino acid transporter 2 (ASCT2) and glucose transporter type 2 (GLUT2) showed a significant increase (P < 0.01). The expression levels of cytokine genes, including IL-8, and IL-1β genes, showed a significant increase (P < 0.05). Furthermore, the expression levels of mitochondrial biogenesis and function-related genes, including mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF), mitochondrial single-strand DNA-binding protein (mt SSB) and mitochondrial polymerase r (mt polr), NADH dehydrogenase subunit 4 (ND4) and cytochrome c oxidase (CcOX) IV, CcOX V and cytochrome c (Cyt c), mammalian silencing information regulator-2α (SIRT-1), glucokinase and citrate synthase (CS), showed a significant increase (P < 0.05). Taken together, the present study indicated that 200 and 2000 ng mL−1 DON could affect proliferation and cell cycle progression from the G2/M phase to the S phase and could mediate the expression levels of differently regulated barrier function, nutrient transport, and mitochondrial biogenesis and function-related genes.

中文翻译:

脱氧雪腐烯醇对IPEC-J2细胞凋亡,屏障功能和营养转运,线粒体生物发生及功能相关基因表达水平的影响

进行这项研究以确定200 ng mL -1和2000 ng mL -1的脱氧雪腐酚(DON)对细胞凋亡,屏障功能,营养转运蛋白基因表达和游离氨基酸变异以及线粒体生物发生和功能相关的影响基因在肠猪上皮细胞系J2(IPEC-J2)中的表达持续6 h,12 h和24 h。暴露于200 ng mL -1 DON会抑制细胞活力,并促进细胞周期从G2 / M期发展到S期(P <0.05)。数据显示,缬氨酸,蛋氨酸,亮氨酸和苯丙氨酸等游离氨基酸的IPEC-J2细胞含量增加了(P<0.05)治疗6小时后;处理12小时后,天冬氨酸,苏氨酸和赖氨酸含量增加(P <0.05);处理24小时后,天冬氨酸,丝氨酸,甘氨酸,丙氨酸,异亮氨酸,亮氨酸和赖氨酸含量降低(P <0.05)。屏障功能基因的表达水平,包括小带闭合(ZO-1),闭合蛋白(OCLN)和claudin 1(CLDN1)的表达水平显着降低(P <0.05)。此外,受不同调节的营养转运蛋白基因,包括B 0,+氨基酸转运蛋白(B 0,+ AT)和钠葡萄糖转运蛋白1(SGLT1)基因的表达水平显着下降(P <0.05)。钠+依赖性中性氨基酸转运蛋白2(ASCT2)和2型葡萄糖转运蛋白(GLUT2)显着增加(P <0.01)。细胞因子基因(包括IL-8和IL-1β基因)的表达水平显着增加(P <0.05)。此外,线粒体生物发生和功能相关基因的表达水平,包括线粒体转录因子A(TFAM)和核呼吸因子-1(NRF),线粒体单链DNA结合蛋白(mt SSB)和线粒体聚合酶r(mt polr),NADH脱氢酶亚基4(ND4)和细胞色素c氧化酶(CcOX)IV,CcOX V和细胞色素c(Cyt c),哺乳动物沉默信息调节剂2α(SIRT-1),葡萄糖激酶和柠檬酸合酶(CS)显着增加(P<0.05)。综上所述,本研究表明200和2000 ng mL -1 DON可以影响从G2 / M期到S期的增殖和细胞周期进程,并可以介导不同调节的屏障功能,营养物质转运和线粒体的表达水平。生物发生和功能相关基因。
更新日期:2017-09-04
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