死亡受体通路在黄曲霉毒素B1致雏鸡胸腺细胞凋亡中的作用

doi:10.11843/j.issn.0366-6964.2017.09.021

摘要/Abstract

摘要：

旨在探究摄食黄曲霉毒素（AF）后，死亡受体通路活化对雏鸡胸腺细胞过度凋亡的信号调控机制。将90只1日龄健康雏鸡随机分为两组，分别饲喂对照日粮和AFB₁日粮（在对照日粮中添加0.6 mg·kg^-1 AFB₁）。于7、14和21日龄时，检测雏鸡胸腺的脏器指数、T淋巴细胞亚群、细胞凋亡率及死亡受体通路上相关基因的mRNA相对转录量。结果显示，与对照组比较，AFB₁组雏鸡胸腺的脏器指数降低，CD3⁺、CD3⁺CD4⁺和CD3⁺CD8⁺ T淋巴细胞的百分率减少，胸腺细胞凋亡率升高，死亡受体通路上RIP1、Caspase-8、Caspase-9、Caspase-3、Fas、FasL、ASK1、IKIP和JNK的mRNA相对转录量升高，Bcl-2、NF-κB1和Bid的mRNA相对转录量降低。本试验中，雏鸡胸腺细胞凋亡上调的过程中，死亡受体通路上的三条下游信号途径均有参与：①通过Fas-FasL-FADD-Caspase-8-Caspase-3途径直接诱导凋亡；②通过Fas-ASK1-JNK-Bcl-2途径，并在线粒体的介导下，启动下游调控因子Caspase-9和Caspase-3诱导细胞凋亡；③通过TNF-α-RIP1-IKIP-NF-κB1-Caspase-3信号途径诱导凋亡。

Abstract:

This experiment was conducted to investigate the regulation mechanism of death receptor pathway involved in the aflatoxins (AF) B₁-induced thymocytes apoptosis. Ninety healthy chickens were randomly divided into two groups, and fed on control diet and AFB₁ containing diet (formulated by adding 0.6 mg·kg^-1 AFB₁ into the control diet) respectively for 21 days. Thymus was sampled for detecting the relative weight, T-cell subsets, percentage of apoptotic cells and relative mRNA expression of genes in the death receptor pathway at 7, 14 and 21 days of age. Our results showed that in the AFB₁ group, the relative weight of thymus was decreased; the percentages of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺ T-cells were decreased, and the percentage of apoptotic thymocytes was increased, when compared with those in the control group. Also, the relative mRNA transcription of RIP1, Caspase-8, Caspase-9, Caspase-3, Fas, FasL, ASK1, IKIP and JNK were up-regulated, and those of Bcl-2, NF-κB1 and Bid were down-regulated. It was speculated that the mechanisms of the excessive apoptosis of thymocytes could be related to the following three downstream death receptor pathways:①AFB₁ could directly induce the apoptosis through the Fas-FasL-FADD-Caspase-8-Caspase-3 pathway; ②Fas could take part in the excessive apoptosis through Fas-ASK1-JNK-Bcl-2 pathway which was mediated via mitochondria; ③The constitutive activation of the TNF-α-RIP1-IKIP-NF-κB1-caspase-3 could be a pathway contributing to the apoptosis of thymocytes induced by AFB₁.

中图分类号:

S856.9

彭西, 梁娜, 方静, 吴邦元. 死亡受体通路在黄曲霉毒素B₁致雏鸡胸腺细胞凋亡中的作用[J]. 畜牧兽医学报, 2017, 48(9): 1744-1752.

PENG Xi, LIANG Na, FANG Jing, WU Bang-yuan. Study on Regulation Mechanism of Death Receptor Pathway Related to Up-regulated Apoptosis of Thymocytes in Broilers after AFB₁ Exposure[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2017, 48(9): 1744-1752.

0
/ / 推荐

导出引用管理器 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

链接本文: https://www.xmsyxb.com/CN/10.11843/j.issn.0366-6964.2017.09.021

https://www.xmsyxb.com/CN/Y2017/V48/I9/1744

参考文献

[1] GOURAMA H, BULLERMAN L B. Aspergillus flavus and Aspergillus parasiticus:aflatoxigenic fungi of concern in foods and feeds:a review[J]. J Food Protect, 1995, 58(12):1395-1404.
[2] SINGHAL K K, KAUR H. Aflatoxins in livestock and poultry:a review[J]. Indian J Anim Sci, 2005, 75(1):113-120.
[3] REDZWAN S M, ROSITA J, SOKHINI A M M, et al. Detection of serum AFB₁-lysine adduct in Malaysia and its association with liver and kidney functions[J]. Int J Hyg Environ Health, 2014, 217(4-5):443-451.
[4] OSWALD I P, MARIN D E, BOUHET S, et al. Immunotoxicological risk of mycotoxins for domestic animals[J]. Food Addit Contam, 2005, 22(4):354-360.
[5] HAN X Y, HUANG Q C, LI W F, et al. Changes in growth performance, digestive enzyme activities and nutrient digestibility of cherry valley ducks in response to aflatoxin B₁ levels[J]. Livest Sci, 2008, 119(1-3):216-220.
[6] PENG X, CHEN K J, CHEN J, et al. Aflatoxin B₁ affects apoptosis and expression of Bax, Bcl-2, and Caspase-3 in thymus and bursa of fabricius in broiler chickens[J]. Environ Toxicol, 2016, 31(9):1113-1120.
[7] 于正强, 陈瑾, 彭西, 等. 黄曲霉毒素B₁对雏鸡免疫器官影响的病理学观察[J]. 畜牧兽医学报, 2015, 46(8):1447-1454.
YU Z Q, CHEN J, PENG X, et al. Effect of aflatoxin B₁ on pathological changes of immune organs in broilers[J]. Acta Veterinaria et Zootechnica Sinica, 2015, 46(8):1447-1454. (in Chinese)
[8] PAUL S, JAKHAR R, BHARDWAJ M, et al. Glutathione-S-transferase omega 1(GSTO1-1) acts as mediator of signaling pathways involved in aflatoxin B₁-induced apoptosis-autophagy crosstalk in macrophages[J]. Free Radical Biol Med, 2015, 89:1218-1230.
[9] GHIMPETT,EANU O M, TOLESCU A, MILITARU M. Aflatoxin and ochratoxin contamination in poultry-a review[J]. Sci Works-Univ Agronom Sci Vet Med Bucharest Ser C, Vet Med, 2012, 58(3):308-317.
[10] TESSARI E N C, OLIVEIRA C A F, CARDOSO A L S P, et al. Effects of aflatoxin B₁ and fumonisin B₁ on body weight, antibody titres and histology of broiler chicks[J]. Br Poult Sci, 2006, 47(3):357-364.
[11] PENG X, YU Z Q, LIANG N, et al. The mitochondrial and death receptor pathways involved in the thymocytes apoptosis induced by aflatoxin B₁[J]. Oncotarget, 2016, 7(11):12222-12234.
[12] JIANG M, PENG X, FANG J, et al. Effects of aflatoxin B₁ on T-cell subsets and mRNA expression of cytokines in the intestine of broilers[J]. Int J Mol Sci, 2015, 16(4):6945-6959.
[13] BAKHEET S A, ATTIA S M, ALWETAID M Y, et al. β-1,3-Glucan reverses aflatoxin B₁-mediated suppression of immune responses in mice[J]. Life Sci, 2016, 152:1-13.
[14] GIRARD N. Thymic epithelial tumours:from basic principles to individualised treatment strategies[J]. Eur Respir Rev, 2013, 22(127):75-87.
[15] NEWTON K, HARRIS A W, BATH M L, et al. A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes[J]. EMBO J, 1998, 17(3):706-718.
[16] CHEN K J, SHU G, PENG X, et al. Protective role of sodium selenite on histopathological lesions, decreased T-cell subsets and increased apoptosis of thymus in broilers intoxicated with aflatoxin B₁[J]. Food Chem Toxicol, 2013, 59:446-454.
[17] HE J, ZHANG K Y, CHEN D W, et al. Effects of vitamin E and selenium yeast on growth performance and immune function in ducks fed maize naturally contaminated with aflatoxin B₁[J]. Livest Sci, 2013, 152(2-3):200-207.
[18] CONTE D, LISTON P, WONG J W, et al. Thymocyte-targeted overexpression of xiap transgene disrupts T lymphoid apoptosis and maturation[J]. Proc Natl Acad Sci U S A, 2001, 98(9):5049-5054.
[19] DAVEY G M, SCHOBER S L, ENDRIZZI B T, et al. Preselection thymocytes are more sensitive to t cell receptor stimulation than mature T cells[J]. J Exp Med, 1998, 188(10):1867-1874.
[20] URBANI S, AMADEI B, FISICARO P, et al. Outcome of acute hepatitis C is related to virus-specific CD4 function and maturation of antiviral memory CD8 responses[J]. Hepatology, 2006, 44(1):126-139.
[21] NOSSAL G J V. Negative selection of lymphocytes[J]. Cell, 1994, 76(2):229-239.
[22] ABBÈS S, BEN SALAH-ABBÈS J, JEBALI R, et al. Interaction of aflatoxin B₁ and fumonisin B₁ in mice causes immunotoxicity and oxidative stress:possible protective role using lactic acid bacteria[J]. J Immunotoxicol, 2016, 13(1):46-54.
[23] SURAI P F, DVORSKA J E. Effects of mycotoxins on antioxidant status and immunity[M]//DIAZ D E. The Mycotoxin Blue Book. Nottingham:Nottingham University Press, 2005:93-137.
[24] KAUFMANN T, STRASSER A, JOST P J. Fas death receptor signalling:roles of Bid and XIAP[J]. Cell Death Differ, 2012, 19(1):42-50.
[25] YANIV G, SHILKRUT M, LARISCH S, et al. Hydrogen peroxide predisposes neonatal rat ventricular myocytes to Fas-mediated apoptosis[J]. Biochem Biophys Res Commun, 2005, 336(3):740-746.
[26] MAUNDRELL K, ANTONSSON B, MAGNENAT E, et al. Bcl-2 undergoes phosphorylation by c-Jun N-terminal kinase/stress-activated protein kinases in the presence of the constitutively active GTP-binding protein Rac1[J]. J Biol Chem, 1997, 272(40):25238-25242.
[27] SLEE E A, KEOGH S A, MARTIN S J. Cleavage of BID during cytotoxic drug and UV radiation-induced apoptosis occurs downstream of the point of Bcl-2 action and is catalysed by caspase-3:a potential feedback loop for amplification of apoptosis-associated mitochondrial cytochrome c release[J]. Cell Death Differ, 2000, 7(6):556-565.
[28] ZHU G Z, WU C J, ZHAO Y G, et al. Optineurin Negatively Regulates TNFα-Induced NF-κB Activation by Competing with NEMO for Ubiquitinated RIP[J]. Curr Biol, 2007, 17(16):1438-1443.
[29] DEVIN A, COOK A, LIN Y, et al. The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1:TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation[J]. Immunity, 2000, 12(4):419-429.
[30] 赵学英. IKIP通过靶向IKKβ负向调节NF-κB介导的炎性细胞因子的表达[D]. 济南:山东大学, 2013.
ZHAO X Y. IκB kinase interacting protein negatively regulates production of proinflammatory cytokines by targeting IKKβ[D]. Jinan:Shandong University, 2013. (in Chinese)
[31] JACKSON-BERNITSAS D G, ICHIKAWA H, TAKADA Y, et al. Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF-κB activation and proliferation in human head and neck squamous cell carcinoma[J]. Oncogene, 2007, 26(10):1385-1397.
[32] HECKMAN C A, MEHEW J W, BOXER L M. NF-κB activates Bcl-2 expression in t(14;18) lymphoma cells[J]. Oncogene, 2002, 21(24):3898-3908.
[33] ZHENG L X, FISHER G, MILLER R E, et al. Induction of apoptosis in mature T cells by tumour necrosis factor[J]. Nature, 1995, 377(6547):348-351.

死亡受体通路在黄曲霉毒素B₁致雏鸡胸腺细胞凋亡中的作用

Study on Regulation Mechanism of Death Receptor Pathway Related to Up-regulated Apoptosis of Thymocytes in Broilers after AFB₁ Exposure

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	谢旖, 邹郦睿, 陶冉, 刘莎, 王江萍, 文利新, 邬静, 王吉. 单宁酸对低剂量T-2毒素诱导小鼠结肠黏膜损伤与菌群失调的保护效应[J]. 畜牧兽医学报, 2023, 54(8): 3582-3594.
[2]	赵阳飞, 于洋欢, 王金明, 张建海, 孙子龙, 牛瑞燕, 王俊东. IL-17A基因敲除对氟诱导小鼠肝炎症反应和肝细胞凋亡的影响[J]. 畜牧兽医学报, 2023, 54(7): 3108-3117.
[3]	赵栋皓, 原梦, 马凯腾, 段卓, 祝一鑫, 唐芳, 韩克光, 霍乃蕊. 羊骨胶原肽对镉的螯合作用及对镉致鸡肝损伤的干预作用[J]. 畜牧兽医学报, 2023, 54(6): 2641-2652.
[4]	颜琼娴, 陈文勋, 惠浩阳, 彭灿, 汤少勋, 周小玲, 谭支良. 玉米赤霉烯酮对山羊生长性能、胃肠道发酵模式和菌群结构的影响研究[J]. 畜牧兽医学报, 2023, 54(3): 1109-1123.
[5]	常颖艳, 赵鸿雁, 胡茂志, 刘宗平. 枸杞酰胺体外对镉致成骨细胞凋亡的保护作用[J]. 畜牧兽医学报, 2023, 54(3): 1273-1280.
[6]	梁文清, 刘忠华, 常晓月, 何婷, 陈嘉, 马晓莉, 唐兆新, 余文兰. 长期高铜暴露通过影响线粒体自噬和细胞焦亡诱导大鼠肝组织损伤[J]. 畜牧兽医学报, 2022, 53(12): 4490-4500.
[7]	仝锡帅, 余耿生, 李雅文, 冉迪, 顾建红, 邹辉, 袁燕, 卞建春, 刘宗平. NAC通过抑制大鼠肺细胞凋亡缓解镉致肺组织损伤[J]. 畜牧兽医学报, 2022, 53(9): 3241-3250.
[8]	季艳菊, 钟高龙, 常晓月, 李英, 胡莲美, 张辉, 潘家强, 唐兆新. 紫锥菊通过调控TLR4-NF-κB通路增强免疫抑制鸡的免疫功能[J]. 畜牧兽医学报, 2022, 53(7): 2354-2363.
[9]	闻双全, 王莉, 张文华, 徐明畅, 邹辉, 顾建红, 刘学忠, 卞建春, 刘宗平, 袁燕. Fas对镉暴露致大鼠大脑皮质自噬体形成的影响[J]. 畜牧兽医学报, 2022, 53(5): 1608-1614.
[10]	张雪晴, 仝锡帅, 王果帅, 卞建春, 刘学忠, 袁燕, 邹辉, 沈小兰, 刘宗平, 顾建红. 葛根素缓解镉对大鼠股骨胫骨中成骨细胞分化的抑制作用[J]. 畜牧兽医学报, 2022, 53(2): 628-636.
[11]	谢志明, 吴春梅, 陈少元, 王照, 王岩. 柴胡多糖通过抑制氧化应激和炎症反应减轻铅诱导小鼠肝肾损伤的研究[J]. 畜牧兽医学报, 2021, 52(9): 2660-2672.
[12]	闻双全, 陈洁, 王莉, 邹辉, 顾建红, 刘学忠, 卞建春, 刘宗平, 袁燕. Fas对镉激活PC12细胞线粒体凋亡通路的影响[J]. 畜牧兽医学报, 2021, 52(8): 2326-2333.
[13]	王莉, 陈洁, 闻双全, 邹辉, 顾建红, 刘学忠, 卞建春, 刘宗平, 袁燕. Fas/FasL通路对镉激活PC12细胞MAPK通路的影响[J]. 畜牧兽医学报, 2021, 52(7): 2034-2043.
[14]	郭蓉, 郭亚洲, 王帅, 杨晨, 苏永霞, 吴晨晨, 路浩, 赵宝玉. 中国天然草地有毒植物及其放牧家畜中毒病研究进展[J]. 畜牧兽医学报, 2021, 52(5): 1171-1185.
[15]	刘冰贤, 曾绮雯, 陈汉明, 庞聪颖, 刘莹炜, 杨必婧, 易江南, 黎远亮, 黎扬威, 唐兆新, 李英, 张辉. 纳米硒对氟化钠诱导小鼠肝组织细胞凋亡的影响[J]. 畜牧兽医学报, 2021, 52(5): 1424-1431.