Cyanobacterial Cyclic Peptides Can Disrupt Cytoskeleton Organization in Human Astrocytes—A Contribution to the Understanding of the Systemic Toxicity of Cyanotoxins
Abstract
:1. Introduction
2. Results
2.1. Interactions of CCPs with the Lipid Monolayer
2.2. Protein Phosphatase Inhibition
2.3. Metabolic Activity
2.4. Gene Expression Analysis
2.5. Cytoskeleton Organization
2.5.1. Light Microscopy
2.5.2. Cytoskeleton Immunostaining
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Cyclic Cyanopeptides
5.2. Interactions of CCPs with Lipid Monolayers
5.3. Protein Phosphatase Inhibition Assay
5.4. Cell Culture
5.5. Metabolic Activity of the Cells
5.6. mRNA Expression Analysis
5.7. Cytoskeleton Immunostaining
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Cheung, M.Y.; Liang, S.; Lee, J. Toxin-Producing Cyanobacteria in Freshwater: A Review of the Problems, Impact on Drinking Water Safety, and Efforts for Protecting Public Health. J. Microbiol. 2013, 51, 1–10. [Google Scholar] [CrossRef]
- Paerl, H.W. Mitigating Harmful Cyanobacterial Blooms in a Human- and Climatically-Impacted World. Life 2014, 4, 988–1012. [Google Scholar] [CrossRef]
- Chorus, I.; Fastner, J.; Welker, M. Cyanobacteria and Cyanotoxins in a Changing Environment: Concepts, Controversies, Challenges. Water 2021, 13, 2463. [Google Scholar] [CrossRef]
- Moreira, C.; Vasconcelos, V.; Antunes, A. Cyanobacterial Blooms: Current Knowledge and New Perspectives. Earth 2022, 3, 127–135. [Google Scholar] [CrossRef]
- Sauvé, S.; Desrosiers, M. A Review of What Is an Emerging Contaminant. Chem. Cent. J. 2014, 8, 15. [Google Scholar] [CrossRef]
- Pouria, S.; De Andrade, A.; Barbosa, J.; Cavalcanti, R.L.; Barreto, V.T.S.; Ward, C.J.; Preiser, W.; Poon, G.K.; Neild, G.H.; Codd, G.A. Fatal Microcystin Intoxication in Haemodialysis Unit in Caruaru, Brazil. Lancet 1998, 352, 21–26. [Google Scholar] [CrossRef]
- Yuan, M.; Carmichael, W.W.; Hilborn, E.D. Microcystin Analysis in Human Sera and Liver from Human Fatalities in Caruaru, Brazil 1996. Toxicon 2006, 48, 627–640. [Google Scholar] [CrossRef]
- Welker, M.; Brunke, M.; Preussel, K.; Lippert, I.; Von Döhren, H. Diversity and Distribution of Microcystis (Cyanobacteria) Oligopeptide Chemotypes from Natural Communities Studied by Single-Colony Mass Spectrometry. Microbiology 2004, 150, 1785–1796. [Google Scholar] [CrossRef]
- Ding, W.-X.; Shen, H.-M.; Zhu, H.-G.; Lee, B.-L.; Ong, C.-N. Genotoxicity of Microcystic Cyanobacteria Extract of a Water Source in China. Mutat. Res./Genet. Toxicol. Environ. Mutagen. 1999, 442, 69–77. [Google Scholar] [CrossRef]
- Honkanen, R.E.; Zwiller, J.; Moore, R.E.; Daily, S.L.; Khatra, B.S.; Dukelow, M.; Boynton, A.L. Characterization of Microcystin-LR, a Potent Inhibitor of Type 1 and Type 2A Protein Phosphatases. J. Biol. Chem. 1990, 265, 19401–19404. [Google Scholar] [CrossRef] [PubMed]
- Pereira, S.R.; Vasconcelos, V.M.; Antunes, A. The Phosphoprotein Phosphatase Family of Ser/Thr Phosphatases as Principal Targets of Naturally Occurring Toxins. Crit. Rev. Toxicol. 2011, 41, 83–110. [Google Scholar] [CrossRef]
- Fischer, W.J.; 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. Pharmacol. 2005, 203, 257–263. [Google Scholar] [CrossRef]
- Toivola, D.M.; Eriksson, J.E. Toxins Affecting Cell Signalling and Alteration of Cytoskeletal Structure. Toxicol. Vitr. 1999, 13, 521–530. [Google Scholar] [CrossRef] [PubMed]
- Fischer, A.; Hoeger, 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 Microcystin Congeners in Vitro: A Comparison of Primary Human Hepatocytes and OATP-Transfected HEK293 Cells. Toxicol. Appl. Pharmacol. 2010, 245, 9–20. [Google Scholar] [CrossRef]
- Suchy, F.J. Hepatocellular Transport of Bile Acids. Semin. Liver Dis. 1993, 13, 235–247. [Google Scholar] [CrossRef] [PubMed]
- Gehringer, M.M. Microcystin-LR and Okadaic Acid-induced Cellular Effects: A Dualistic Response. FEBS Lett. 2004, 557, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Batista, T.; De Sousa, G.; Suput, J.S.; Rahmani, R.; Šuput, D. Microcystin-LR Causes the Collapse of Actin Filaments in Primary Human Hepatocytes. Aquat. Toxicol. 2003, 65, 85–91. [Google Scholar] [CrossRef]
- Eleršek, T.; Bláha, L.; Mazur-Marzec, H.; Schmidt, W.; Carmeli, S. Other Cyanobacterial Bioactive Substances. In Handbook of Cyanobacterial Monitoring and Cyanotoxin Analysis; John Wiley & Sons, Ltd.: West Sussex, UK, 2016; pp. 179–195. ISBN 978-1-119-06876-1. [Google Scholar]
- Grach-Pogrebinsky, O.; Sedmak, B.; Carmeli, S. Protease Inhibitors from a Slovenian Lake Bled Toxic Waterbloom of the Cyanobacterium Planktothrix rubescens. Tetrahedron 2003, 59, 8329–8336. [Google Scholar] [CrossRef]
- Harada, K.-I.; Fujii, K.; Shimada, T.; Suzuki, M.; Sano, H.; Adachi, K.; Carmichael, W.W. Two Cyclic Peptides, Anabaenopeptins, a Third Group of Bioactive Compounds from the cyanobacterium Anabaena Flos-Aquae NRC 525-17. Tetrahedron Lett. 1995, 36, 1511–1514. [Google Scholar] [CrossRef]
- Gkelis, S.; Lanaras, T.; Sivonen, K. The Presence of Microcystins and Other Cyanobacterial Bioactive Peptides in Aquatic Fauna Collected from Greek Freshwaters. Aquat. Toxicol. 2006, 78, 32–41. [Google Scholar] [CrossRef]
- Bubik, A.; Sedmak, B.; Novinec, M.; Lenarčič, B.; Lah, T.T. Cytotoxic and Peptidase Inhibitory Activities of Selected Non-Hepatotoxic Cyclic Peptides from Cyanobacteria. Biol. Chem. 2008, 389, 1339–1346. [Google Scholar] [CrossRef] [PubMed]
- Spoof, L.; Błaszczyk, A.; Meriluoto, J.; Cegłowska, M.; Mazur-Marzec, H. Structures and Activity of New Anabaenopeptins Produced by Baltic Sea Cyanobacteria. Mar. Drugs 2015, 14, 8. [Google Scholar] [CrossRef]
- Schreuder, H.; Liesum, A.; Lönze, P.; Stump, H.; Hoffmann, H.; Schiell, M.; Kurz, M.; Toti, L.; Bauer, A.; Kallus, C.; et al. Isolation, Co-Crystallization and Structure-Based Characterization of Anabaenopeptins as Highly Potent Inhibitors of Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa). Sci. Rep. 2016, 6, 32958. [Google Scholar] [CrossRef]
- Chlipala, G.E.; Mo, S.; Orjala, J. Chemodiversity in Freshwater and Terrestrial Cyanobacteria—A Source for Drug Discovery. Curr. Drug Targets 2011, 12, 1654–1673. [Google Scholar] [CrossRef]
- 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 Pt 1, 23–33. [Google Scholar] [CrossRef] [PubMed]
- Aillaud, C.; Bosc, C.; Peris, L.; Bosson, A.; Heemeryck, P.; Van Dijk, J.; Le Friec, J.; Boulan, B.; Vossier, F.; Sanman, L.E.; et al. Vasohibins/SVBP Are Tubulin Carboxypeptidases (TCPs) That Regulate Neuron Differentiation. Science 2017, 358, 1448–1453. [Google Scholar] [CrossRef]
- Barlič, A.; Gutiérrez-Aguirre, I.; Caaveiro, J.M.M.; Cruz, A.; Ruiz-Argüello, M.-B.; Pérez-Gil, J.; González-Mañas, J.M. Lipid Phase Coexistence Favors Membrane Insertion of Equinatoxin-II, a Pore-Forming Toxin from Actinia Equina. J. Biol. Chem. 2004, 279, 34209–34216. [Google Scholar] [CrossRef]
- Eiríksdóttir, E.; Konate, K.; Langel, Ü.; Divita, G.; Deshayes, S. Secondary Structure of Cell-Penetrating Peptides Controls Membrane Interaction and Insertion. Biochim. Et Biophys. Acta (BBA) Biomembr. 2010, 1798, 1119–1128. [Google Scholar] [CrossRef] [PubMed]
- Yoshizawa, S.; Matsushima, R.; Watanabe, M.F.; Harada, K.-I.; Ichihara, A.; Carmichael, W.W.; Fujiki, H. Inhibition of Protein Phosphatases by Microcystis and Nodularin Associated with Hepatotoxicity. J. Cancer Res. Clin. Oncol. 1990, 116, 609–614. [Google Scholar] [CrossRef] [PubMed]
- Xu, S.; Yi, X.; Liu, W.; Zhang, C.; Massey, I.Y.; Yang, F.; Tian, L. A Review of Nephrotoxicity of Microcystins. Toxins 2020, 12, 693. [Google Scholar] [CrossRef] [PubMed]
- Yi, X.; Xu, S.; Huang, F.; Wen, C.; Zheng, S.; Feng, H.; Guo, J.; Chen, J.; Feng, X.; Yang, F. Effects of Chronic Exposure to Microcystin-LR on Kidney in Mice. Int. J. Environ. Res. Public Health 2019, 16, 5030. [Google Scholar] [CrossRef]
- Lin, H.; Liu, W.; Zeng, H.; Pu, C.; Zhang, R.; Qiu, Z.; Chen, J.-A.; Wang, L.; Tan, Y.; Zheng, C.; et al. Determination of Environmental Exposure to Microcystin and Aflatoxin as a Risk for Renal Function Based on 5493 Rural People in Southwest China. Environ. Sci. Technol. 2016, 50, 5346–5356. [Google Scholar] [CrossRef]
- Li, X.; Xu, L.; Zhou, W.; Zhao, Q.; Wang, Y. Chronic Exposure to Microcystin-LR Affected Mitochondrial DNA Maintenance and Caused Pathological Changes of Lung Tissue in Mice. Environ. Pollut. 2016, 210, 48–56. [Google Scholar] [CrossRef]
- Soares, R.M.; Cagido, V.R.; Ferraro, R.B.; Meyer-Fernandes, J.R.; Rocco, P.R.M.; Zin, W.A.; Azevedo, S.M.F.O. Effects of Microcystin-LR on Mouse Lungs. Toxicon 2007, 50, 330–338. [Google Scholar] [CrossRef]
- Wu, J.-X.; Huang, H.; Yang, L.; Zhang, X.-F.; Zhang, S.-S.; Liu, H.-H.; Wang, Y.-Q.; Yuan, L.; Cheng, X.-M.; Zhuang, D.-G.; et al. Gastrointestinal Toxicity Induced by Microcystins. World J. Clin. Cases 2018, 6, 344–354. [Google Scholar] [CrossRef]
- Cao, L.; Huang, F.; Massey, I.Y.; Wen, C.; Zheng, S.; Xu, S.; Yang, F. Effects of Microcystin-LR on the Microstructure and Inflammation-Related Factors of Jejunum in Mice. Toxins 2019, 11, 482. [Google Scholar] [CrossRef]
- Cao, L.; Massey, I.Y.; Feng, H.; Yang, F. A Review of Cardiovascular Toxicity of Microcystins. Toxins 2019, 11, 507. [Google Scholar] [CrossRef]
- Xiong, Q.; Xie, P.; Li, H.; Hao, L.; Li, G.; Qiu, T.; Liu, Y. Acute Effects of Microcystins Exposure on the Transcription of Antioxidant Enzyme Genes in Three Organs (Liver, Kidney, and Testis) of Male Wistar Rats. J. Biochem. Mol. Toxicol. 2010, 24, 361–367. [Google Scholar] [CrossRef]
- Milutinović, A.; Živin, M.; Zorc-Pleskovič, R.; Sedmak, B.; Šuput, D. Nephrotoxic Effects of Chronic Administration of Microcystins -LR and -YR. Toxicon 2003, 42, 281–288. [Google Scholar] [CrossRef]
- Hinojosa, M.G.; Gutiérrez-Praena, D.; Prieto, A.I.; Guzmán-Guillén, R.; Jos, A.; Cameán, A.M. Neurotoxicity Induced by Microcystins and Cylindrospermopsin: A Review. Sci. Total Environ. 2019, 668, 547–565. [Google Scholar] [CrossRef] [PubMed]
- Hu, Y.; Chen, J.; Fan, H.; Xie, P.; He, J. A Review of Neurotoxicity of Microcystins. Environ. Sci. Pollut. Res. 2016, 23, 7211–7219. [Google Scholar] [CrossRef]
- Yan, M.; Jin, H.; Pan, C.; Hang, H.; Li, D.; Han, X. Movement Disorder and Neurotoxicity Induced by Chronic Exposure to Microcystin-LR in Mice. Mol. Neurobiol. 2022, 59, 5516–5531. [Google Scholar] [CrossRef]
- Runnegar, M.T.; Kong, S.; Berndt, N. Protein Phosphatase Inhibition and in Vivo Hepatotoxicity of Microcystins. Am. J. Physiol. Gastrointest. Liver Physiol. 1993, 265, G224–G230. [Google Scholar] [CrossRef]
- Yang, F.; Wen, C.; Zheng, S.; Yang, S.; Chen, J.; Feng, X. Involvement of MAPK/ERK1/2 Pathway in Microcystin-Induced Microfilament Reorganization in HL7702 Hepatocytes. J. Toxicol. Environ. Health Part A 2018, 81, 1135–1141. [Google Scholar] [CrossRef]
- Shi, L.; Du, X.; Liu, H.; Chen, X.; Ma, Y.; Wang, R.; Tian, Z.; Zhang, S.; Guo, H.; Zhang, H. Update on the Adverse Effects of Microcystins on the Liver. Environ. Res. 2021, 195, 110890. [Google Scholar] [CrossRef]
- Li, T.; Fan, X.; Cai, M.; Jiang, Y.; Wang, Y.; He, P.; Ni, J.; Mo, A.; Peng, C.; Liu, J. Advances in Investigating Microcystin-Induced Liver Toxicity and Underlying Mechanisms. Sci. Total Environ. 2023, 905, 167167. [Google Scholar] [CrossRef]
- Bulc Rozman, K.; Jurič, D.M.; Šuput, D. Selective Cytotoxicity of Microcystins LR, LW and LF in Rat Astrocytes. Toxicol. Lett. 2017, 265, 1–8. [Google Scholar] [CrossRef]
- Filipič, M.; Žegura, B.; Sedmak, B.; Horvat-Žnidaršič, I.; Milutinovič, A.; Šuput, D. Subchronic Exposure of Rats to Sublethal Dose of Microcystin-YR Induces DNA Damage in Multiple Organs. Radiol. Oncol. 2007, 41, 15–22. [Google Scholar] [CrossRef]
- Li, X.-B.; Zhang, X.; Ju, J.; Li, Y.; Yin, L.; Pu, Y. Alterations in Neurobehaviors and Inflammation in Hippocampus of Rats Induced by Oral Administration of Microcystin-LR. Environ. Sci. Pollut. Res. 2014, 21, 12419–12425. [Google Scholar] [CrossRef]
- 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, 326–337. [Google Scholar] [CrossRef]
- Vesterkvist, P.S.M.; Meriluoto, J.A.O. Interaction between Microcystins of Different Hydrophobicities and Lipid Monolayers. Toxicon 2003, 41, 349–355. [Google Scholar] [CrossRef]
- Vesterkvist, P.S.M.; Misiorek, J.O.; Spoof, L.E.M.; Toivola, D.M.; Meriluoto, J.A.O. Comparative Cellular Toxicity of Hydrophilic and Hydrophobic Microcystins on Caco-2 Cells. Toxins 2012, 4, 1008–1023. [Google Scholar] [CrossRef] [PubMed]
- Grach-Pogrebinsky, O.; Sedmak, B.; Carmeli, S. Seco[d-Asp3]microcystin-RR and [d-Asp3,d-Glu(OMe)6]microcystin-RR, Two New Microcystins from a Toxic Water Bloom of the Cyanobacterium Planktothrix rubescens. J. Nat. Prod. 2004, 67, 337–342. [Google Scholar] [CrossRef]
- Eriksson, J.E.; Grönberg, L.; Nygård, S.; Slotte, J.P.; Meriluoto, J.A.O. Hepatocellular Uptake of 3H-Dihydromicrocystin-LR, a Cyclic Peptide Toxin. Biochim. Et Biophys. Acta (BBA) Biomembr. 1990, 1025, 60–66. [Google Scholar] [CrossRef]
- Máthé, C.; Beyer, D.; M-Hamvas, M.; Vasas, G. The Effects of Microcystins (Cyanobacterial Heptapeptides) on the Eukaryotic Cytoskeletal System. Mini Rev. Med. Chem. 2016, 16, 1063–1077. [Google Scholar] [CrossRef] [PubMed]
- Zhou, M.; Tu, W.-W.; Xu, J. Mechanisms of Microcystin-LR-Induced Cytoskeletal Disruption in Animal Cells. Toxicon 2015, 101, 92–100. [Google Scholar] [CrossRef]
- Toivola, D.M.; Eriksson, J.E.; Brautigan, D.L. Identification of Protein Phosphatase 2A as the Primary Target for microcystin-LR in Rat Liver Homogenates. FEBS Lett. 1994, 344, 175–180. [Google Scholar] [CrossRef]
- Contín, M.A.; Purro, S.A.; Bisig, C.G.; Barra, H.S.; Arce, C.A. Inhibitors of Protein Phosphatase 1 and 2A Decrease the Level of Tubulin Carboxypeptidase Activity Associated with Microtubules. Eur. J. Biochem. 2003, 270, 4921–4929. [Google Scholar] [CrossRef]
- Panda, D.; DeLuca, K.; Williams, D.; Jordan, M.A.; Wilson, L. Antiproliferative Mechanism of Action of Cryptophycin-52: Kinetic Stabilization of Microtubule Dynamics by High-Affinity Binding to Microtubule Ends. Proc. Natl. Acad. Sci. USA 1998, 95, 9313–9318. [Google Scholar] [CrossRef]
- Pekny, M.; Lane, E.B. Intermediate Filaments and Stress. Exp. Cell Res. 2007, 313, 2244–2254. [Google Scholar] [CrossRef]
- Pekny, M.; Nilsson, M. Astrocyte Activation and Reactive Gliosis. Glia 2005, 50, 427–434. [Google Scholar] [CrossRef]
- Toivola, D.M.; Omary, M.B.; Ku, N.; Peltola, O.; Baribault, H.; Eriksson, J.E. Protein Phosphatase Inhibition in Normal and Keratin 8/18 Assembly-Incompetent Mouse Strains Supports a Functional Role of Keratin Intermediate Filaments in Preserving Hepatocyte Integrity. Hepatology 1998, 28, 116–128. [Google Scholar] [CrossRef] [PubMed]
- Herrmann, H.; Aebi, U. Intermediate Filaments and Their Associates: Multi-Talented Structural Elements Specifying Cytoarchitecture and Cytodynamics. Curr. Opin. Cell Biol. 2000, 12, 79–90. [Google Scholar] [CrossRef] [PubMed]
- Toivola, D.M.; Tao, G.-Z.; Habtezion, A.; Liao, J.; Omary, M.B. Cellular Integrity plus: Organelle-Related and Protein-Targeting Functions of Intermediate Filaments. Trends Cell Biol. 2005, 15, 608–617. [Google Scholar] [CrossRef] [PubMed]
- Eriksson, J.E.; Paatero, G.I.L.; Meriluoto, J.A.O.; Codd, G.A.; Kass, G.E.N.; Nicotera, P.; Orrenius, S. Rapid Microfilament Reorganization Induced in Isolated Rat Hepatocytes by Microcystin-LR, a Cyclic Peptide Toxin. Exp. Cell Res. 1989, 185, 86–100. [Google Scholar] [CrossRef]
- Hooser, S.B.; Beasley, V.R.; Waite, L.L.; Kuhlenschmidt, M.S.; Carmichael, W.W.; Haschek, W.M. Actin Filament Alterations in Rat Hepatocytes Induced In Vivo and In Vitro by Microcystin-LR, a Hepatotoxin from the Blue-Green Alga, Microcystis aeruginosa. Vet. Pathol. 1991, 28, 259–266. [Google Scholar] [CrossRef]
- Runnegar, M.T.C.; Falconer, I.R. Effect of Toxin from the Cyanobacterium Microcystis Aeruginosa on Ultrastructural Morphology and Actin Polymerization in Isolated Hepatocytes. Toxicon 1986, 24, 109–115. [Google Scholar] [CrossRef]
- Jordan, M.A.; Wilson, L. Microtubules as a Target for Anticancer Drugs. Nat. Rev. Cancer 2004, 4, 253–265. [Google Scholar] [CrossRef] [PubMed]
- Volterra, A.; Meldolesi, J. Astrocytes, from Brain Glue to Communication Elements: The Revolution Continues. Nat. Rev. Neurosci. 2005, 6, 626–640. [Google Scholar] [CrossRef] [PubMed]
- Sedmak, B.; Eleršek, T.; Grach-Pogrebinsky, O.; Carmeli, S.; Sever, N.; Lah, T. Ecotoxicologically Relevant Cyclic Peptides from Cyanobacterial Bloom (Planktothrix Rubescens)—A Threat to Human and Environmental Health. Radiol. Oncol. 2008, 42, 102–113. [Google Scholar] [CrossRef]
- An, J.; Carmichael, W.W. Use of a Colorimetric Protein Phosphatase Inhibition Assay and Enzyme Linked Immunosorbent Assay for the Study of Microcystins and Nodularins. Toxicon 1994, 32, 1495–1507. [Google Scholar] [CrossRef] [PubMed]
- Mosmann, T. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. J. Immunol. Methods 1983, 65, 55–63. [Google Scholar] [CrossRef] [PubMed]
- Harada, K.-I.; Matsuura, K.; Suzuki, M.; Watanabe, M.F.; Oishi, S.; Dahlem, A.M.; Beasley, V.R.; Carmichael, W.W. Isolation and Characterization of the Minor Components Associated with Microcystins LR and RR in the Cyanobacterium (Blue-Green Algae). Toxicon 1990, 28, 55–64. [Google Scholar] [CrossRef] [PubMed]
CCP | IC50 (µM) | |
---|---|---|
PP1 | PP2A | |
PP BL1125 | 131.5 ± 87.5 | 18.2 ± 15.7 |
AnP-B | 9.5 ± 0.9 | 12.3 ± 6.1 |
AnP-F | 28.2 ± 3.4 | 1.0 ± 0.2 |
MC-LR | 0.0050 ± 0.0016 | 0.000048 ± 0.00001 |
(A) | |||||
---|---|---|---|---|---|
Gene | CCP (µM) | PP BL1125 | AnP-B | AnP-F | MC-LR |
TUBA1A | 0 | 1.005 ± 0.013 | 1.005 ± 0.013 | 1.005 ± 0.013 | 1.004 ± 0.097 |
0.1 | 0.940 ± 0.162 | 1.082 ± 0.219 | 0.941 ± 0.186 | 0.957 ± 0.046 | |
1 | 0.824 ± 0.128 ** | 0.807 ± 0.100 *** | 1.144 ± 0.291 | 0.941 ± 0.025 | |
10 | 1.000 ± 0.141 | 0.895 ± 0.119 * | 0.826 ± 0.036 *** | / | |
ACTB | 0 | 1.010 ± 0.022 | 1.010 ± 0.022 | 1.010 ± 0.022 | 1.016 ± 0.204 |
0.1 | 0.949 ± 0.140 | 1.175 ± 0.386 | 0.824 ± 0.227 | 1.071 ± 0.437 | |
1 | 0.988 ± 0.147 | 0.935 ± 0.157 | 1.121 ± 0.167 | 1.866 ± 0.844 | |
10 | 1.162 ± 0.251 | 0.934 ± 0.166 | 0.890 ± 0.184 | / | |
NES | 0 | 1.001 ± 0.002 | 1.001 ± 0.002 | 1.001 ± 0.002 | 1.032 ± 0.299 |
0.1 | 1.262 ± 0.077 *** | 1.361 ± 0.291 * | 1.345 ± 0.205 ** | 0.917 ± 0.067 | |
1 | 1.203 ± 0.196 * | 1.221 ± 0.338 | 1.449 ± 0.171 *** | 1.266 ± 0.250 | |
10 | 1.370 ± 0.208 ** | 1.388 ± 0.313 * | 1.381 ± 0.173 *** | / | |
GFAP | 0 | 1.011 ± 0.019 | 1.011 ± 0.019 | 1.011 ± 0.019 | 1.086 ± 0.503 |
0.1 | 1.051 ± 0.351 | 1.053 ± 0.124 | 1.326 ± 0.507 | 1.395 ± 0.312 | |
1 | 0.947 ± 0.101 | 1.434 ± 0.180 ** | 0.846 ± 0.211 | 1.453 ± 0.279 | |
10 | 1.119 ± 0.240 | 0.918 ± 0.204 | 1.167 ± 0.250 | / | |
(B) | |||||
Gene | CCP (µM) | PP BL1125 | AnP-B | AnP-F | MC-LR |
TUBA1A | 0 | 1.001 ± 0.002 | 1.001 ± 0.002 | 1.001 ± 0.002 | 1.001 ± 0.001 |
0.1 | 1.124 ± 0.050 * | 1.131 ± 0.031 ** | 1.016 ± 0.098 | 1.031 ± 0.064 | |
1 | 1.094 ± 0.172 | 1.098 ± 0.192 | 1.023 ± 0.160 | 0.983 ± 0.099 | |
10 | 1.171 ± 0.049 ** | 1.429 ± 0.068 *** | 1.354 ± 0.126 ** | / | |
ACTB | 0 | 1.003 ± 0.005 | 1.003 ± 0.005 | 1.003 ± 0.005 | 1.002 ± 0.002 |
0.1 | 1.015 ± 0.057 | 0.998 ± 0.070 | 0.935 ± 0.118 | 1.466 ± 0.286 ** | |
1 | 1.051 ± 0.185 | 1.039 ± 0.070 | 1.084 ± 0.138 | 1.796 ± 0.277 *** | |
10 | 1.147 ± 0.105 | 1.122 ± 0.033 ** | 1.046 ± 0.130 | / | |
NES | 0 | 1.000 ± 0.001 | 1.000 ± 0.001 | 1.000 ± 0.001 | 1.001 ± 0.001 |
0.1 | 1.003 ± 0.164 | 0.948 ± 0.143 | 1.040 ± 0.105 | 1.030 ± 0.105 | |
1 | 1.069 ± 0.105 | 0.992 ± 0.085 | 1.081 ± 0.056 | 0.877 ± 0.148 | |
10 | 1.240 ± 0.041 ** | 0.931 ± 0.054 | 0.886 ± 0.037 ** | / | |
GFAP | 0 | 1.010 ± 0.015 | 1.010 ± 0.015 | 1.010 ± 0.015 | 1.005 ± 0.005 |
0.1 | 1.107 ± 0.214 | 1.088 ± 0.390 | 1.002 ± 0.087 | 0.986 ± 0.120 | |
1 | 1.283 ± 0.185 | 1,109 ± 0.215 | 1.096 ± 0.211 | 0.909 ± 0.052 ** | |
10 | 1.016 ± 0.046 | 1.175 ± 0.148 | 1.191 ± 0.435 | / |
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Bubik, A.; Frangež, R.; Žužek, M.C.; Gutiérrez-Aguirre, I.; Lah, T.T.; Sedmak, B. Cyanobacterial Cyclic Peptides Can Disrupt Cytoskeleton Organization in Human Astrocytes—A Contribution to the Understanding of the Systemic Toxicity of Cyanotoxins. Toxins 2024, 16, 374. https://doi.org/10.3390/toxins16090374
Bubik A, Frangež R, Žužek MC, Gutiérrez-Aguirre I, Lah TT, Sedmak B. Cyanobacterial Cyclic Peptides Can Disrupt Cytoskeleton Organization in Human Astrocytes—A Contribution to the Understanding of the Systemic Toxicity of Cyanotoxins. Toxins. 2024; 16(9):374. https://doi.org/10.3390/toxins16090374
Chicago/Turabian StyleBubik, Anja, Robert Frangež, Monika C. Žužek, Ion Gutiérrez-Aguirre, Tamara T. Lah, and Bojan Sedmak. 2024. "Cyanobacterial Cyclic Peptides Can Disrupt Cytoskeleton Organization in Human Astrocytes—A Contribution to the Understanding of the Systemic Toxicity of Cyanotoxins" Toxins 16, no. 9: 374. https://doi.org/10.3390/toxins16090374