Involvement of endoplasmic reticulum and autophagy in microcystin-LR toxicity in Vero-E6 and HepG2 cell lines

Toxicology in Vitro

Volumn 27, Issue 1, 2013, Pages 138-148

  Menezes, Carina ^a   Alverca, Elsa ^a   Dias, Elsa ^a   Sam Bento, Filomena ^a   Pereira, Paulo ^a  

^a NATIONAL INSTITUTE OF HEALTH DR RICARDO JORGE   (Portugal)

Author keywords

Autophagy; Endoplasmic reticulum; HepG2 cells; Lysosomes; Microcystin LR; Vero E6 cells

Indexed keywords

CELL PROTEIN; GLUCOSE REGULATED PROTEIN 94; LIGHT CHAIN 3 ISOFORM B PROTEIN; MICROCYSTIN LR; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; AUTOPHAGY; CELL DISRUPTION; CELL STRAIN HEPG2; CELL SURVIVAL; CELL ULTRASTRUCTURE; CELL VIABILITY; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; CYTOSKELETON; CYTOTOXICITY TEST; DOWN REGULATION; ENDOPLASMIC RETICULUM; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE MICROSCOPY; LONG TERM EXPOSURE; LYSOSOME; MITOCHONDRIAL MEMBRANE; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; VERO CELL;

ANIMALS; AUTOPHAGY; CELL SURVIVAL; CERCOPITHECUS AETHIOPS; ENDOPLASMIC RETICULUM; HEP G2 CELLS; HUMANS; LYSOSOMES; MEMBRANE GLYCOPROTEINS; MICROCYSTINS; MICROTUBULE-ASSOCIATED PROTEINS; MITOCHONDRIA; VERO CELLS;

EID: 84869431500     PISSN: 08872333     EISSN: 18793177     Source Type: Journal    
DOI: 10.1016/j.tiv.2012.09.009     Document Type: Article

References (82)

1. Alverca E., Andrade M., Dias E., Sam-Bento F., Batoréu M.C.C., Jordan P., Silva M.J., Pereira P. Morphological and ultrastructural effects of microcystin-LR from Microcystis aeruginosa extract on a kidney cell line. Toxicon 2009, 54:283-294.
2. 2 is a consequence of lysosomal rupture. Biochem. J. 2001, 356:549-555.
3. Argon Y., Simen B.B. GRP94, an ER chaperone with protein and peptide binding properties. Semin. Cell Dev. Biol. 1999, 10(5):495-505.
4. Atencio L., Moreno I., Prieto A.I., Moyano R., Molina A.M., Cameán A.M. Acute effects of microcystins MC-LR and MC-RR on acid and alkaline phosphatase activities and pathological changes in intraperitoneally exposed tilapia fish (Oreochromis sp.). Toxicol. Pathol. 2008, 36:449-458.
5. Barth S., Glick D., Macleod K.F. Autophagy: assays and artifacts. J. Pathol. 2010, 221(2):117-124.
6. Bedard K., MacDonald N., Collins J., Cribb A. Cytoprotection following endoplasmic reticulum stress protein induction in continuous cell lines. Basic Clin. Pharmacol. Toxicol. 2004, 94:124-131.
7. Billam M., Mukhi S., Tang L., Weimin G., Wang J.S. Toxic response indicators of microcystin-LR in F344 rats following a single dose treatment. Toxicon 2008, 51:1068-1080.
8. Boaru D.A., Dragos N., Schirmer K. Microcystin-LR induced cellular effects in mammalian and fish primary hepatocytes cultures and cell lines: a comparative study. Toxicology 2006, 218:134-148.
9. Borenfreund E., Puerner J. Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol. Lett. 1985, 24:119-124.
10. Carmichael W.W. Cyanobacteria secondary metabolites - the cyanotoxins. J. Appl. Bacteriol. 1992, 72:445-459.
11. Chen T., Wang Q., Cui J., Yang W., Shi Q., Hua Z., Ji J., Shen P. Induction of apoptosis in mouse liver by microcystin-LR. A combined transcriptomic, proteomic and simulation strategy. Mol. Cell. Proteomics 2005, 4:958-974.
12. Chen R., Dai R.Y., Duan C.Y., Liu Y.P., Chen S.K., Yan D.M., Chen C.N., Wei M., Li H. Unfolded protein response suppresses cisplatin-induced apoptosis via autophagy regulation in human hepatocellular carcinoma cells. Folia Biol. (Praha) 2011, 57:87-95.
13. Chong M., Gu K., Lam P., Yang M., Fong W. Study on the cytotoxicity of microcystin-LR on cultured cells. Chemosphere 2000, 41:143-147.
14. Chorus I., Falconer I.R., Salas H.J., Bartram J. Heath risks caused by freshwater cyanobacteria in recreational waters. J. Toxicol. Environ. Health, Part B 2000, 3:323-347.
15. Codogno P., Meijer A.J. Autophagy and signaling: their role in cell survival and cell death. Cell Death Different 2005, 12:1509-1518.
16. Cribb A.E., Peyrou M., Muruganandan S., Schneider L. The endoplasmic reticulum in xenobiotic toxicity. Drug Metab. Rev. 2005, 37(3):405-442.
17. Dey A., Kessova I.G., Cederbaum A.I. Decreased protein and mRNA expression of ER stress proteins GRP78 and GRP94 in HepG2 cells over-expressing CYP2E1. Arch. Biochem. Biophys. 2006, 447:155-166.
18. Dias E., Andrade M., Alverca E., Pereira P., Batoréu M.C.C., Jordan P., Silva M.J. Comparative study of the cytotoxic effect of microcystin-LR and purified extracts from M. aeruginosa on a kidney cell line. Toxicon 2009, 53:457-495.
19. Dias E., Matos P., Pereira P., Batoréu M.C.C., Silva M.J., Jordan P. Microcystin-LR activates the ERK1/2 kinases and stimulates the proliferation of the monkey kidney-derived cell line Vero-E6. Toxicol. In Vitro 2010, 24(6):1689-1695.
20. Ding W., Shen H., Ong C. Critical role of reactive oxygen species and mitochondrial permeability transition in microcystin-induced rapid apoptosis in rat hepatocytes. Hepatology 2000, 32:547-555.
21. Ding W., Shen H., Ong C. Calpain activation after mitochondrial permeability transition in microcystin-induced cell death in rat hepatocytes. Biochem. Biophys. Res. Commun. 2002, 291:321-331.
22. Ding W., Ong C. Role of oxidative stress and mitochondrial changes in cyanobacteria-induced apoptosis and hepatotoxicity. FEMS Microbiol. Lett. 2003, 220(1):1-7.
23. Ding W., Ni H.M., Gao W., Hou Y.F., Melan M.A., Chen X., Stolz D.B., Shao Z.M., Yin X.M. Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival. J. Biol. Chem. 2007, 282(7):4702-4710.
24. Eskelinen E.-L. Doctor Jekyll and Mister Hyde: autophagy can promote both cell survival and cell death. Cell Death Different. 2005, 12:1468-1472.
25. Faria G., Cardoso C.R.B., Larson R.E., Silva J.S., Rossi M.A. Chlorhexidine-induced apoptosis or necrosis in L929 fibroblasts: a role for endoplasmic reticulum stress. Toxicol. Appl. Pharmacol. 2009, 234(2):256-265.
26. Fisher A., Heoger S.J., Stemmer K., Feurstein D.J., Knobeloch D., Nussler A., Dietrich D.R. The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystins congeners in vitro: a comparison of primary human hepatocytes and OATP-transfected HEK293 cells. Toxicol. Appl. Pharmacol. 2010, 245(1):9-20.
27. Fischer W.L., Altheimer S., Cattori V., Meier P.J., Dietrich D.R., Hagenbuch B. Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin. Toxicol. Appl. Phamacol. 2005, 203:257-263.
28. Gupta N., Pant S.C., Vijayaraghavan R., Rao P.V.L. Comparative toxicity evaluation of cyanobacterial cyclic peptide toxin microcystin variants (LR, RR, YR) in mice. Toxicology 2003, 188:285-296.
29. Hagenbuch B., Meier P.J. The superfamily of organic anion transporting polypeptides. Biochem. Biophys. Acta 2003, 1609:1-18.
30. Herfindal L., Selheim F. Microcystin produces disparate effects on liver cells in a dose dependent manner. Mini-Rev. Med. Chem. 2006, 6:279-285.
31. Hooser S.B., Beasley V.R., Lovell R.A., Carmichael W.W., Haschek W.M. Toxicity of microcystin LR, a cyclic heptapeptide hepatotoxin from Microcystis aeruginosa, to rats and mice. Vet. Pathol. 1989, 26:246.
32. Hooser S.B., Beasley V.R., Basgall E.J., Carmichael W.W., Haschek W.M. Microcystin-LR-induced ultrastructural changes in rats. Vet. Pathol. 1990, 27:9.
33. Hooser S. Fulminant hepatocyte apoptosis in vivo following microcystin-LR administration to rats. Toxicol. Pathol. 2000, 28(5):726-733.
34. Huang P., Zheng Y., Xu L. Oral administration of cyanobacterial bloom extract induced the altered expression of the PP2A, Bax, and Bcl-2 in mice. Environ. Toxicol. 2008, 23:688-693.
35. Ito E., Kondo F., Harada K. Hepatic necrosis in aged mice by oral administration of microcystin-LR. Toxicon 1997, 35(2):231-239.
36. Kabeya Y., Mizushima N., Ueno T., Yamamoto A., Kirisako T., Noda T., Ohsumi Y., Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000, 19:5720-5728.
37. Khan S.A., Ghosh S., Wickstrom M., Miller L.A., Hess R., Haschek W.M., Beasley V.R. Comparative pathology of microcystin-LR in cultured hepatocytes, fibroblasts and renal epithelial cells. Nat. Toxicol. 1995, 3:119-128.
38. Kim R., Emi M., Tanabe K. Role of mitochondria as the gardens of cell death. Cancer Chemother. Pharmacol. 2006, 57:545-553.
39. Kullak-Ublick G.A., Beuers U., Paumgartner G. Molecular and functional characterization of bile acid transport in human hepatoblastoma HepG2 Cells. Hepatology 1996, 23:1053-1060.
40. Kurtz T., Terman A., Gustafsson B., Brunk U.T. Lysosomes and oxidative stress in aging and apoptosis. Biochem. Biophys. Acta 2008, 1780:1291-1303.
41. La-Salete R., Oliveira M.M., Palmeira C.A., Almeida J., Peixoto F.P. Mitochondria a key role in microcystin-LR kidney intoxication. J. Appl. Toxicol. 2008, 28:55-62.
42. Li W., Yuan X.M., Nordgren G., Dalen H., Dubwchik G.M., Firestone R.A., Brunk U.T. Induction of cell death by the lysosomotropic detergent MSDH. FEBS Lett. 2000, 470:35-39.
43. Li X., Liu Y., Song L. Cytological alterations in isolated hepatocytes from common carp (Cyprinus carpio L.) exposed to microcystin-LR. Environ. Toxicol. 2001, 16(6):517-522.
44. Li L., Xie P., Chen J. Biochemical and ultrastructural changes of the liver and kidney of the phytoplanktivorous silver carp feeding naturally on toxic Microcystis blooms in Taihu Lake, China. Toxicon 2007, 49:1042-1053.
45. Liang J., Li T., Zhang Y., Guo Z., Xu L. Effect of microcystin-LR on protein phosphatase 2A and its function in human amniotic epithelial cells. J Zhejiang Univ-Sci B (Biomed. & Biotechnol.) 2011, 12(12):951-960.
46. Lowe J., Souza-Menezes J., Freire D.S., Mattos L.J., Castiglione R.C., Barbosa C.M.L., Santiago L., Ferrão F.M., Cardoso L.H.D., Silva R.T., Vieira-Beiral H.J., Vieyra A., Morales M.M., Azevedo S.M.F.O., Soareset R.M. Single sublethal dose of microcystin-LR is responsible for different alterations in biochemical, histological and physiological renal parameters. Toxicon 2012, 59:601-609.
47. MacKintosh C., Beattie K.A., Klumpp S., Cohen P., Codd G.A. Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. Fed. Eur. Biochem. Soc. 1990, 264:187-192.
48. Maiuri M.C., Zalckvar E., Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Mol. Cell Biol. 2007, 8:741-752.
49. Malécot M., Mezhoud K., Marie A., Praseuth D., Puiseux-Dao S., Edery M. Proteomic study of the effects of microcystin-LR on organelle and membrane proteins in medaka fish liver. Aquat. Toxicol. 2009, 94(2):153-161.
50. Mankiewicz J., Tarczynska M., Fladmark K.E., Doskeland S.O., Walter Z., Zalewski M. Apoptotic effect of cyanobacterial extract on rat hepatocytes and human lymphocytes. Environ. Toxicol. 2001, 16:225-233.
51. McDermott C.M., Nho C.W., Howard W., Holtons B. The cyanobacterial toxin, microcystin-LR, can induce apoptosis in a variety of cell types. Toxicon 1998, 36(12):1981-1996.
52. Meijer A.J., Codogno P. Regulation and role of autophagy in mammalian cells. Int. J. Biochem. Cell Biol. 2004, 36:2445-2462.
53. Milutinović A., Živina M., Zorc-Pleskovič R., Sedmak B., Šuput D. Nephrotoxic effects of chronic administration of microcystins-LR and -YR. Toxicon 2003, 42:281-288.
54. Miura G.A., Robinson N.A., Geisbert T.W., Bostian K.A., White J.D., Pace J.G. Comparision of in vivo and in vitro toxic effects of mirocystin-LR in fasted rats. Toxicon 1989, 27(11):1229-1240.
55. Miura G.A., Robinson N.A., Lawrence W.B., Pace J.G. Hepatotoxicity of microcystin-LR in fed and fasted rats. Toxicon 1991, 29(3):337-346.
56. Mizushima N., Ohsumi Y., Yoshimori T. Autophagosome formation in mammalian cells. Cell Struct. Funct. 2002, 27:412-429.
57. Monks N.R., Liu S., Xu Y., Yu H., Bendelow A.S., Moscow J.A. Potent cytotoxicity of the phosphatase inhibitor Microcystin-LR and microcystin analogues in OATP1B1- and OATP1B3-expressing HeLa cells. Mol. Cancer Therap. 2007, 6:587-598.
58. Nobre A.C.L., Jorge M.C.M., Menezes D.B., Fonteles M.C., Monteiro H.S.A. Effects of microcystin-LR in isolated perfused rat kidney. Braz. J. Med. Biol. Res. 1999, 32:985-988.
59. Nong Q., Komatsu M., Izumo K., Indo H.P., Xu B., Aoyama K., Majima H.J., Horiuchi M., Morimoto K., Takeuchi T. Involvement of reactive oxygen species in Microcystin-LR-induced cytogenotoxicity. Free Rad. Res. 2007, 41:1326-1337.
60. Osswald J., Carvalho A.P., Claro J., Vasconcelos V. Effects of cyanobacterial extracts containing anatoxin-a and of pure anatoxin-a on early developmental stages of carp. Ecotoxicol. Environ. Saf. 2008, 72(2):473-478.
61. Paulino S., Sam-Bento F., Churro C., Alverca E., Dias E., Valério E., Pereira P. The Estela Sousa e Silva algal culture collection: a resource of biological and toxicological interest. Hydrobiologia 2009, 636:489-492.
62. Philips H.J. Dye exclusion tests for cell viability. Tissue Culture: Methods and Applications 1973, 406-408. Academic Press, New York. P.F. Kruse, M.K. Patterson (Eds.).
63. Qin W., Xu X., Zhang X., Wang Y., Meng X., Miao A., Yang L. Endoplasmic reticulum stress in murine liver and kidney exposed to microcystin-LR. Toxicon 2010, 56:1334-1341.
64. Qin W., Yang L., Zhang X., Zhang Z., Xu L., Wu J., An J., Wang Y. Cyanobacteria-blooming water samples from Lake Taihu induce endoplasmic reticulum stress in liver and kidney of mice. Ecotoxicology 2012, 10.1007/s10646-012-0903-6.
65. Pietsch C., Wiegand C., Amé M.V., Nicklisch A., Wunderlin D., Pflugmacher S. The effects of a cyanobacterial crude extract on different aquatic organisms: evidence for cyanobacterial toxin modulating factors. Environ. Toxicol. 2001, 16:535-542.
66. Rao R.V., Ellerby H.M., Bredesen D.E. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 2004, 11(4):372-380.
67. 2+-binding and antiapoptotic properties is a novel proteolytic target of calpain during etoposide-induced apoptosis. J. Biol. Chem. 1999, 274(40):28476-28483.
68. Ribble D., Goldstein N.B., Norris D.A., Shellman Y.G. A simple technique for quantifying apoptosis in 96-well plates. BMC Biotechnol. 2005, 5:12-18.
69. Rovetta F., Stacchiotti A., Consiglio A., Cadei M., Grigolato P.G., Lavazza A., Rezzani R., Aleo M.F. ER signaling regulation drives the switch between autophagy and apoptosis in NRK-52E cells exposed to cisplatin. Exp. Cell Res. 2012, 318:238-250.
70. Ryan P.M., Bedard K., Breining T., Cribb A.E. Disruption of the endoplasmic reticulum by cytotoxins in LLC-PK1 cells. Toxicol. Lett. 2005, 159:154-163.
71. Stacchiotti A., Morandini F., Bettoni F., Schena I., Lavazza A., Grigolato P.G., Apostoli P., Rezzani R., Aleo M.F. Stress proteins and oxidative damage in a renal derived cell line exposed to inorganic mercury and lead. Toxicology 2009, 264:215-224.
72. Terasaki M., Chen L.B., Fujiwara K. Microtubules and the endoplasmic reticulum are highly interdependent structures. J. Cell Biol. 1986, 103(4):1557-1568.
73. Toivola D.M., Goldman R.D., Garrod D.R., Eriksson J.E. Protein phosphatases maintain the organization and structural interactions of hepatic keratin intermediate filaments. J. Cell Sci. 1997, 110:23-33.
74. Valério E., Chambel L., Paulino S., Faria N., Pereira P., Tenreiro R. Multiplex PCR for detection of microcystins-producing cyanobacteria from freshwater samples. Environ. Toxicol. 2010, 25(3):251-260.
75. Wang Q., Xie P., Chen J., Liang G. Distribution of microcystins in various organs (heart, liver, intestine, gonad, brain, kidney and lung) of Wistar rat via intravenous injection. Toxicon 2008, 52:721-727.
76. Weng D., Lu Y., Wei Y., Liu Y., Shen P. The role of ROS in microcystin-LR-induced hepatocytes apoptosis and liver injury in mice. Toxicology 2007, 232:15-23.
77. Wera S., Hemmings B.A. Serine/threonine protein phosphatases. Biochem. J. 1995, 311:17-29.
78. Wickstrom M.L., Khan S.A., Haschek W.M., Wyman J.F., Eriksson J.E., Schaeffer D.J., Beasley V.R. Alterations in microtubules, intermediate filaments, and microfilaments induced by microcystin-LR in cultured cells. Toxicol. Pathol. 1995, 23(3):326-337.
79. Wilkening S., Stahl F., Bader A. Comparison of primary human hepatocytes and hepatoma cell line HepG2 with regard to their biotransformation properties. Drug Metab. Dispos. 2003, 31:1035-1042.
80. Žegura B., Sedmak B., Filipič M. Microcystin-LR induces oxidative DNA damage in human hepatoma cell line HepG2. Toxicon 2003, 41:41-48.
81. Žegura B., Lah T.T., Filipič M. The role of reactive oxygen species in microcystin-LR-induced DNA damage. Toxicology 2004, 200:59-68.
82. Žegura B., Lah T.T., Filipič M. Alteration of intracellular GSH levels and its role in microcystin-LR-induced DNA damage in human hepatoma HepG2 cells. Mut. Res. 2006, 611:25-33.