刘林,
林长高,
隗黎丽,
江西农业大学动物科学技术学院, 南昌 330045
作者简介: 何丽(1995-),女,硕士研究生,研究方向为鱼类免疫学,E-mail:lihejxyc@163.com.
通讯作者: 隗黎丽,hbliliwei@163.com
基金项目: 国家自然科学基金资助项目（31760764，31460146）中图分类号: X171.5
Research Progress on Autophagy Induced by Microcystins
He Li,Liu Lin,
Lin Changgao,
Wei Lili,
College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Corresponding author: Wei Lili,hbliliwei@163.com
CLC number: X171.5
-->
摘要
HTML全文
图
参考文献
相关文章
施引文献
资源附件
访问统计
摘要:微囊藻毒素是由蓝藻产生的次生代谢产物，具有很强的肝毒性、肾毒性、生殖毒性及神经毒性等。而自噬作为维持细胞稳态的自我更新机制，在应对有毒物质胁迫时发挥着重要作用，最新的研究报道表明微囊藻毒素可诱导细胞自噬。目前，微囊藻毒素诱导细胞自噬的研究，主要以肝细胞、肾细胞、性腺细胞及神经细胞为研究对象。本文综述了微囊藻毒素对上述细胞自噬诱导的研究进展，且从氧化应激途径和内质网应激途径探讨微囊藻毒素诱导细胞自噬的机制，并对今后研究方向进行了展望，可为全面剖析微囊藻毒素的毒性机理以及自噬在其中发挥的具体作用提供参考。
关键词: 微囊藻毒素/
自噬/
氧化应激/
内质网应激
Abstract:Microcystins, the secondary metabolites produced by cyanobacteria, have strong hepatotoxicity, renal toxicity, reproductive toxicity, neurotoxicity, etc. Autophagy is considered to be a self-renewal mechanism to maintain cell homeostasis, and plays important roles under toxic stress. The latest researches indicate that microcystins can induce the autophagy. At present, the studies on autophagy induced by microcystins mainly focused on hepatocytes, renal cells, gonadal cells and neurocytes, which are summarized in this review. Besides, the mechanisms of autophagy induced by microcystins have been investigated from oxidative stress and endoplasmic reticulum stress signaling pathways. Moreover, the further studies on autophagy induced by microcystins are prospected in the present paper. Overall, this review will provide references for the comprehensive analysis of the toxic mechanisms of microcystins as well as the specific role of autophagy.
Key words:microcystins/
autophagy/
oxidative stress/
endoplasmic reticulum stress.
| Massey I Y, Yang F, Ding Z, et al. Exposure routes and health effects of microcystins on animals and humans:A mini-review[J]. Toxicon, 2018, 151:156-162 |
| Ikehara T, Nakashima J, Nakashima S, et al. Different responses of primary normal human hepatocytes and human hepatoma cells toward cyanobacterial hepatotoxin microcystin-LR[J]. Toxicon, 2015, 105:4-9 |
| Campos A, Vasconcelos V. Molecular mechanisms of microcystin toxicity in animal cells[J]. International Journal of Molecular Sciences, 2010, 11(1):268-287 |
| Muzzio A M, Noyes P D, Stapleton H M, et al. Tissue distribution and thyroid hormone effects on mRNA abundance for membrane transporters Mct8, Mct10, and organic anion-transporting polypeptides (Oatps) in a teleost fish[J]. Comparative Biochemistry and Physiology Part A:Molecular & Integrative Physiology, 2014, 167:77-89 |
| Yang X H, Liu W Y, Lin H, et al. Interaction effects of AFB1 and MC-LR co-exposure with polymorphism of metabolic genes on liver damage:Focusing on SLCO1B1 and GSTP1[J]. Scientific Reports, 2017, 7(1):16164 |
| Wang Z K, Li G Y, Wu Q, et al. Microcystin-LR exposure induced nephrotoxicity by triggering apoptosis in female zebrafish[J]. Chemosphere, 2019, 214:598-605 |
| Meng X N, Peng H R, Ding Y Z, et al. A transcriptomic regulatory network among miRNAs, piRNAs, circRNAs, lncRNAs and mRNAs regulates microcystin-leucine arginine (MC-LR)-induced male reproductive toxicity[J]. The Science of the Total Environment, 2019, 667:563-577 |
| Wang J, Zhang C L, Zhu J L, et al. Blood-brain barrier disruption and inflammation reaction in mice after chronic exposure to Microcystin-LR[J]. The Science of the Total Environment, 2019, 689:662-678 |
| Dikic I. Proteasomal and autophagic degradation systems[J]. Annual Review of Biochemistry, 2017, 86:193-224 |
| Bhat P, Kriel J, Shubha Priya B, et al. Modulating autophagy in cancer therapy:Advancements and challenges for cancer cell death sensitization[J]. Biochemical Pharmacology, 2018, 147:170-182 |
| Tekirdag K, Cuervo A M. Chaperone-mediated autophagy and endosomal microautophagy:Joint by a chaperone[J]. The Journal of Biological Chemistry, 2018, 293(15):5414-5424 |
| Feng Y C, Yao Z Y, Klionsky D J. How to control self-digestion:Transcriptional, post-transcriptional, and post-translational regulation of autophagy[J]. Trends in Cell Biology, 2015, 25(6):354-363 |
| Swart C, Du Toit A, Loos B. Autophagy and the invisible line between life and death[J]. European Journal of Cell Biology, 2016, 95(12):598-610 |
| Liu T Z, Mazmouz R, Neilan B A. An in vitro and in vivo study of broad-range phosphopantetheinyl transferases for heterologous expression of cyanobacterial natural products[J]. ACS Synthetic Biology, 2018, 7(4):1143-1151 |
| Puddick J, Prinsep M R, Wood S A, et al. Further characterization of glycine-containing microcystins from the McMurdo dry Valleys of Antarctica[J]. Toxins, 2015, 7(2):493-515 |
| Rastogi R P, Sinha R P, Incharoensakdi A. The cyanotoxin-microcystins:Current overview[J]. Reviews in Environmental Science and Bio/Technology, 2014, 13(2):215-249 |
| Puddick J, Prinsep M R, Wood S A, et al. High levels of structural diversity observed in microcystins from Microcystis CAWBG11 and characterization of six new microcystin congeners[J]. Marine Drugs, 2014, 12(11):5372-5395 |
| Mohamed Z A, Deyab M A, Abou-Dobara M I, et al. Occurrence of cyanobacteria and microcystin toxins in raw and treated waters of the Nile River, Egypt:Implication for water treatment and human health[J]. Environmental Science and Pollution Research, 2015, 22(15):11716-11727 |
| Xing Y N, Xu Y H, Chen Y, et al. Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins[J]. Cell, 2006, 127(2):341-353 |
| Garda T, Kónya Z, Freytag C, et al. Allyl-isothiocyanate and microcystin-LR reveal the protein phosphatase mediated regulation of metaphase-anaphase transition in Vicia faba[J]. Frontiers in Plant Science, 2018, 9:1823 |
| Wang B L, Liu J H, Huang P, et al. Protein phosphatase 2A inhibition and subsequent cytoskeleton reorganization contributes to cell migration caused by microcystin-LR in human laryngeal epithelial cells (Hep-2)[J]. Environmental Toxicology, 2017, 32(3):890-903 |
| Chen L, Li S C, Guo X C, et al. The role of GSH in microcystin-induced apoptosis in rat liver:Involvement of oxidative stress and NF-κB[J]. Environmental Toxicology, 2016, 31(5):552-560 |
| Liu W Y, Wang L Q, Zheng C F, et al. Microcystin-LR increases genotoxicity induced by aflatoxin B1 through oxidative stress and DNA base excision repair genes in human hepatic cell lines[J]. Environmental Pollution, 2018, 233:455-463 |
| Lin W, Guo H H, Wang L K, et al. Waterborne microcystin-LR exposure induced chronic inflammatory response via MyD88-dependent toll-like receptor signaling pathway in male zebrafish[J]. The Science of the Total Environment, 2020, 702:134969 |
| Chen H Q, Zhao J, Li Y, et al. Gene expression network regulated by DNA methylation and microRNA during microcystin-leucine arginine induced malignant transformation in human hepatocyte L02 cells[J]. Toxicology Letters, 2018, 289:42-53 |
| Chen Y, Zhou Y, Wang X T, et al. Microcystin-LR induces autophagy and apoptosis in rat Sertoli cells in vitro[J]. Toxicon, 2013, 76:84-93 |
| Fischer A, Hoeger S J, Stemmer K, et al. The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro:A comparison of primary human hepatocytes and OATP-transfected HEK293 cells[J]. Toxicology and Applied Pharmacology, 2010, 245(1):9-20 |
| Zhao S J, Xie P, Chen J, et al. A proteomic study on liver impairment in rat pups induced by maternal microcystin-LR exposure[J]. Environmental Pollution, 2016, 212:197-207 |
| Shuai Y, Lou D, Yin J X, et al. Characterization of microcystin-induced dualistic toxic effects on primary rat hepatocytes[J]. Journal of Environmental Pathology, Toxicology and Oncology:Official Organ of the International Society for Environmental Toxicology and Cancer, 2017, 36(1):15-27 |
| Shi Y, Jiang J L, Shan Z J, et al. Oxidative stress and histopathological alterations in liver of Cyprinus carpio L. induced by intraperitoneal injection of microcystin-LR[J]. Ecotoxicology, 2015, 24(3):511-519 |
| Qiao Q, Djediat C, Huet H, et al. Subcellular localization of microcystin in the liver and the gonads of medaka fish acutely exposed to microcystin-LR[J]. Toxicon, 2019, 159:14-21 |
| Zhang H J, Cai C C, Fang W D, et al. Oxidative damage and apoptosis induced by microcystin-LR in the liver of Rana nigromaculata in vivo[J]. Aquatic Toxicology, 2013, 140-141:11-18 |
| Dabholkar A S, Carmichael W W. Ultrastructural changes in the mouse liver induced by hepatotoxin from the freshwater cyanobacterium Microcystis aeruginosa strain 7820[J]. Toxicon, 1987, 25(3):285-292 |
| Menezes C, Alverca E, Dias E, et al. Involvement of endoplasmic reticulum and autophagy in microcystin-LR toxicity in Vero-E6 and HepG2 cell lines[J]. Toxicology in Vitro, 2013, 27(1):138-148 |
| 吴珍, 张亚, 贝云成, 等. 微囊藻毒素-LR对小鼠肝细胞线粒体功能的影响[J]. 现代生物医学进展, 2014, 14(2):226-229Wu Z, Zhang Y, Bei Y C, et al. Exploring the effects of MC-LR on mitochondrial function in mouse liver[J]. Progress in Modern Biomedicine, 2014, 14(2):226-229(in Chinese) |
| Yin J, Wagner D J, Prasad B, et al. Renal secretion of hydrochlorothiazide involves organic anion transporter 1/3, organic cation transporter 2, and multidrug and toxin extrusion protein 2-K[J]. American Journal of Physiology Renal Physiology, 2019, 317(4):F805-F814 |
| Alverca E, Andrade M, Dias E, et al. Morphological and ultrastructural effects of microcystin-LR from Microcystis aeruginosa extract on a kidney cell line[J]. Toxicon, 2009, 54(3):283-294 |
| Lin W, Guo H H, Li Y F, et al. Single and combined exposure of microcystin-LR and nitrite results in reproductive endocrine disruption via hypothalamic-pituitary-gonadal-liver axis[J]. Chemosphere, 2018, 211:1137-1146 |
| Adegoke E O, Adeniran S O, Zeng Y, et al. Pharmacological inhibition of TLR4/NF-κB with TLR4-IN-C34 attenuated microcystin-leucine arginine toxicity in bovine Sertoli cells[J]. Journal of Applied Toxicology, 2019, 39(6):832-843 |
| Zhang S S, Liu C R, Li Y, et al. Novel role of ER stress and autophagy in microcystin-LR induced apoptosis in Chinese hamster ovary cells[J]. Frontiers in Physiology, 2016, 7:527 |
| Liu H H, Zhang X F, Zhang S S, et al. Oxidative stress mediates microcystin-LR-induced endoplasmic reticulum stress and autophagy in KK-1 cells and C57BL/6 mice ovaries[J]. Frontiers in Physiology, 2018, 9:1058 |
| Wang J, Chen Y B, Zhang C L, et al. Learning and memory deficits and Alzheimer's disease-like changes in mice after chronic exposure to microcystin-LR[J]. Journal of Hazardous Materials, 2019, 373:504-518 |
| Yang Y, Wen C, Zheng S L, et al. Influence of microcystins-LR (MC-LR) on autophagy in human neuroblastoma SK-N-SH cells[J]. Journal of Toxicology and Environmental Health Part A, 2019, 82(21):1129-1136 |
| 谭瑶, 邱志群, 黄玉晶, 等. 微囊藻毒素暴露对PC12细胞的影响[C]. 沈阳:环境与健康学术会议——精准环境健康:跨学科合作的挑战, 2018 |
| Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy[J]. Nature Reviews Molecular Cell Biology, 2018, 19(6):349-364 |
| Johnson C E, Tee A R. Exploiting cancer vulnerabilities:MTOR, autophagy, and homeostatic imbalance[J]. Essays in Biochemistry, 2017, 61(6):699-710 |
| Maejima Y, Isobe M, Sadoshima J. Regulation of autophagy by Beclin1 in the heart[J]. Journal of Molecular and Cellular Cardiology, 2016, 95:19-25 |
| Cordani M, Butera G, Pacchiana R, et al. Molecular interplay between mutant p53 proteins and autophagy in cancer cells[J]. Biochimica et Biophysica Acta Reviews on Cancer, 2017, 1867(1):19-28 |
| Stothert A R, Fontaine S N, Sabbagh J J, et al. Targeting the ER-autophagy system in the trabecular meshwork to treat glaucoma[J]. Experimental Eye Research, 2016, 144:38-45 |
| Rahal A, Kumar A, Singh V, et al. Oxidative stress, prooxidants, and antioxidants:The interplay[J]. BioMed Research International, 2014, 2014:761264 |
| Zhao Y Q, Qu T G, Wang P Q, et al. Unravelling the relationship between macroautophagy and mitochondrial ROS in cancer therapy[J]. Apoptosis, 2016, 21(5):517-531 |
| Li L L, Tan J, Miao Y Y, et al. ROS and autophagy:Interactions and molecular regulatory mechanisms[J]. Cellular and Molecular Neurobiology, 2015, 35(5):615-621 |
| Gurusamy N, Das D K. Autophagy, redox signaling, and ventricular remodeling[J]. Antioxidants & Redox Signaling, 2009, 11(8):1975-1988 |
| Tripathi D N, Zhang J W, Jing J, et al. A new role for ATM in selective autophagy of peroxisomes (pexophagy)[J]. Autophagy, 2016, 12(4):711-712 |
| Zhang J H, Zhang C, Jiang X P, et al. Involvement of autophagy in hypoxia-BNIP3 signaling to promote epidermal keratinocyte migration[J]. Cell Death & Disease, 2019, 10(3):234 |
| Zabirnyk O, Liu W, Khalil S, et al. Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy[J]. Carcinogenesis, 2010, 31(3):446-454 |
| Mahdi A A, Rizvi S H, Parveen A. Role of endoplasmic reticulum stress and unfolded protein responses in health and diseases[J]. Indian Journal of Clinical Biochemistry, 2016, 31(2):127-137 |
| Coffey M J, Jennison C, Tonkin C J, et al. Role of the ER and Golgi in protein export by Apicomplexa[J]. Current Opinion in Cell Biology, 2016, 41:18-24 |
| Chen H Y, Yang H L, Pan L, et al. The molecular mechanisms of XBP-1 gene silencing on IRE1α-TRAF2-ASK1-JNK pathways in oral squamous cell carcinoma under endoplasmic reticulum stress[J]. Biomedecine & Pharmacotherapie, 2016, 77:108-113 |
| Cebollero E, Reggiori F, Kraft C. Reticulophagy and ribophagy:Regulated degradation of protein production factories[J]. International Journal of Cell Biology, 2012, 2012:182834 |
| Avivar-Valderas A, Bobrovnikova-Marjon E, Alan Diehl J, et al. Regulation of autophagy during ECM detachment is linked to a selective inhibition of mTORC1 by PERK[J]. Oncogene, 2013, 32(41):4932-4940 |
| Song S L, Tan J, Miao Y Y, et al. Intermittent-hypoxia-induced autophagy activation through the ER-stress-related PERK/eIF2α/ATF4 pathway is a protective response to pancreatic β-cell apoptosis[J]. Cellular Physiology and Biochemistry, 2018, 51(6):2955-2971 |
| B'Chir W, Maurin A C, Carraro V, et al. The eIF2 alpha/ATF4 pathway is essential for stress-induced autophagy gene expression[J]. Nucleic Acids Research, 2013, 41(16):7683-7699 |
| Deegan S, Saveljeva S, Gorman A M, et al. Stress-induced self-cannibalism:On the regulation of autophagy by endoplasmic reticulum stress[J]. Cellular and Molecular Life Sciences, 2013, 70(14):2425-2441 |
| Bootman M D, Chehab T, Bultynck G, et al. The regulation of autophagy by calcium signals:Do we have a consensus?[J]. Cell Calcium, 2018, 70:32-46 |
| Steiner K, Zimmermann L, Hagenbuch B, et al. Zebrafish Oatp-mediated transport of microcystin congeners[J]. Archives of Toxicology, 2016, 90(5):1129-1139 |
