Neuroprotective effect of ATM/ATR inhibitor CGK733 on acrylamide-induced inhibition of cytotoxic effects and neurite outgrowth in PC12 cells
Main Article Content
Abstract
Acrylamide is a neurological and reproductive toxicant for both humans and laboratory animals. It inhibits cellular differentiations in variant cells in vitro. We investigated whether the DNA damage response (DDR) pathway is involved in the inhibition of neurite outgrowth and the induction of cytotoxicity by acrylamide in PC12 cells. In this study, CGK733 (ataxia telangiectasia mutated kinase (ATM) and ATM-related kinase (ATR) inhibitor) was used in inhibition of the DDR pathway, which was induced by acrylamide exposure. The results showed that NGF triggered neurite outgrowth and proliferation of PC12 cells. Both neurite outgrowth and cell proliferation induced by NGF were attenuated after acrylamide exposure. The acrylamide-decreased neurite outgrowth and cell proliferation were increased in the administrations of CGK733. In the NGF-stimulated PC12 cells, CGK733 attenuated acrylamide-induced cell cycle alterations and cellular apoptosis. Moreover, the DDR-related molecules were estimated by Western blotting. The results showed that CGK733 can reverse not only acrylamide-induced expressions of ATM, ATR, and p21 but also acrylamide-decreased expression of cyclin D1 in the NGF-stimulated PC12 cells. These results demonstrated that acrylamide exposure induced the DDR pathway in the NGF-stimulated neurite outgrowth of PC12 cells. Acrylamide-induced inhibition of neurite outgrowth and cytotoxicity in NGF-stimulated PC12 cells can be attenuated by CGK733.
Keywords:
: neurite outgrowth, acrylamide, NGF, CGK733, PC12 cells
Article Details
How to Cite
CHEN, Jong-Hang; CHIU, Ing-Ming; KAO, Chien-Yu.
Neuroprotective effect of ATM/ATR inhibitor CGK733 on acrylamide-induced inhibition of cytotoxic effects and neurite outgrowth in PC12 cells.
Medical Research Archives, [S.l.], v. 6, n. 11, nov. 2018.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1866>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v6i11.1866.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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33. Spencer JP, Vauzour D, Rendeiro C. Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects. Archives of biochemistry and biophysics. 2009;492:1-9.
34. Honda K, Shimohama S, Sawada H, Kihara T, Nakamizo T, Shibasaki H, et al. Nongenomic antiapoptotic signal transduction by estrogen in cultured cortical neurons. Journal of neuroscience research. 2001;64:466-75.
35. Leinninger GM, Backus C, Uhler MD, Lentz SI, Feldman EL. Phosphatidylinositol 3-kinase and Akt effectors mediate insulin-like growth factor-I neuroprotection in dorsal root ganglia neurons. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2004;18:1544-6.
36. Ng YP, Cheung ZH, Ip NY. STAT3 as a downstream mediator of Trk signaling and functions. The Journal of biological chemistry. 2006;281:15636-44.
37. Halliwell B. Oxidative stress and neurodegeneration: where are we now? Journal of neurochemistry. 2006;97:1634-58.
38. Jang JH, Surh YJ. Protective effects of resveratrol on hydrogen peroxide-induced apoptosis in rat pheochromocytoma (PC12) cells. Mutation research. 2001;496:181-90.
39. Rodriguez H, Holmquist GP, D'Agostino R, Jr., Keller J, Akman SA. Metal ion-dependent hydrogen peroxide-induced DNA damage is more sequence specific than metal specific. Cancer research. 1997;57:2394-403.
40. Mehri S, Abnous K, Mousavi SH, Shariaty VM, Hosseinzadeh H. Neuroprotective Effect of Crocin on Acrylamide-induced Cytotoxicity in PC12 cells. Cellular and Molecular Neurobiology. 2012;32:227-35.
2. Kutting B, Schettgen T, Schwegler U, Fromme H, Uter W, Angerer J, et al. Acrylamide as environmental noxious agent: a health risk assessment for the general population based on the internal acrylamide burden. International journal of hygiene and environmental health. 2009;212:470-80.
3. Rice JM. The carcinogenicity of acrylamide. Mutation research. 2005;580:3-20.
4. Chen JH, Lee DC, Chen MS, Ko YC, Chiu IM. Inhibition of neurosphere formation in neural stem/progenitor cells by acrylamide. Cell transplantation. 2015;24:779-96.
5. Garey J, Ferguson SA, Paule MG. Developmental and behavioral effects of acrylamide in Fischer 344 rats. Neurotoxicology and teratology. 2005;27:553-63.
6. Koyama N, Sakamoto H, Sakuraba M, Koizumi T, Takashima Y, Hayashi M, et al. Genotoxicity of acrylamide and glycidamide in human lymphoblastoid TK6 cells. Mutation research. 2006;603:151-8.
7. Svensson K, Abramsson L, Becker W, Glynn A, Hellenas KE, Lind Y, et al. Dietary intake of acrylamide in Sweden. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2003;41:1581-6.
8. LoPachin RM, Ross JF, Lehning EJ. Nerve terminals as the primary site of acrylamide action: a hypothesis. Neurotoxicology. 2002;23:43-59.
9. LoPachin RM, Schwarcz AI, Gaughan CL, Mansukhani S, Das S. In vivo and in vitro effects of acrylamide on synaptosomal neurotransmitter uptake and release. Neurotoxicology. 2004;25:349-63.
10. LoPachin RM. Acrylamide neurotoxicity: neurological, morhological and molecular endpoints in animal models. Advances in experimental medicine and biology. 2005;561:21-37.
11. Jiang L, Cao J, An Y, Geng C, Qu S, Jiang L, et al. Genotoxicity of acrylamide in human hepatoma G2 (HepG2) cells. Toxicology in vitro : an international journal published in association with BIBRA. 2007;21:1486-92.
12. Keith CT, Schreiber SL. PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints. Science (New York, NY). 1995;270:50-1.
13. Smith CJ, Perfetti TA, Rumple MA, Rodgman A, Doolittle DJ. "IARC Group 2B carcinogens" reported in cigarette mainstream smoke. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2001;39:183-205.
14. Chen JH, Tsou TC, Chiu IM, Chou CC. Proliferation inhibition, DNA damage, and cell-cycle arrest of human astrocytoma cells after acrylamide exposure. Chemical research in toxicology. 2010;23:1449-58.
15. Tibbetts RS, Brumbaugh KM, Williams JM, Sarkaria JN, Cliby WA, Shieh SY, et al. A role for ATR in the DNA damage-induced phosphorylation of p53. Genes & development. 1999;13:152-7.
16. Chen JH, Lee DC, Chiu IM. Cytotoxic effects of acrylamide in nerve growth factor or fibroblast growth factor 1-induced neurite outgrowth in PC12 cells. Archives of toxicology. 2014;88:769-80.
17. Chen JH, Chou CC. Acrylamide inhibits cellular differentiation of human neuroblastoma and glioblastoma cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2015;82:27-35.
18. Won J, Kim M, Kim N, Ahn JH, Lee WG, Kim SS, et al. Small molecule-based reversible reprogramming of cellular lifespan. Nature chemical biology. 2006;2:369-74.
19. Alao JP, Sunnerhagen P. The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation. Radiation oncology (London, England). 2009;4:51.
20. Greene LA. Nerve growth factor prevents the death and stimulates the neuronal differentiation of clonal PC12 pheochromocytoma cells in serum-free medium. The Journal of cell biology. 1978;78:747-55.
21. Greene LA, Aletta JM, Rukenstein A, Green SH. PC12 pheochromocytoma cells: culture, nerve growth factor treatment, and experimental exploitation. Methods in enzymology. 1987;147:207-16.
22. Lin WF, Chen CJ, Chang YJ, Chen SL, Chiu IM, Chen L. SH2B1beta enhances fibroblast growth factor 1 (FGF1)-induced neurite outgrowth through MEK-ERK1/2-STAT3-Egr1 pathway. Cellular signalling. 2009;21:1060-72.
23. Rydel RE, Greene LA. Acidic and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells. The Journal of neuroscience : the official journal of the Society for Neuroscience. 1987;7:3639-53.
24. Vaudry D, Stork PJ, Lazarovici P, Eiden LE. Signaling pathways for PC12 cell differentiation: making the right connections. Science (New York, NY). 2002;296:1648-9.
25. Goldstein M, Roos WP, Kaina B. Apoptotic death induced by the cyclophosphamide analogue mafosfamide in human lymphoblastoid cells: contribution of DNA replication, transcription inhibition and Chk/p53 signaling. Toxicology and applied pharmacology. 2008;229:20-32.
26. Chen JH, Yang CH, Wang YS, Lee JG, Cheng CH, Chou CC. Acrylamide-induced mitochondria collapse and apoptosis in human astrocytoma cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2013;51:446-52.
27. Klaunig JE. Acrylamide carcinogenicity. Journal of agricultural and food chemistry. 2008;56:5984-8.
28. Segerback D, Calleman CJ, Schroeder JL, Costa LG, Faustman EM. Formation of N-7-(2-carbamoyl-2-hydroxyethyl)guanine in DNA of the mouse and the rat following intraperitoneal administration of [14C]acrylamide. Carcinogenesis. 1995;16:1161-5.
29. Martins C, Oliveira NG, Pingarilho M, Gamboa da Costa G, Martins V, Marques MM, et al. Cytogenetic damage induced by acrylamide and glycidamide in mammalian cells: correlation with specific glycidamide-DNA adducts. Toxicological sciences : an official journal of the Society of Toxicology. 2007;95:383-90.
30. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell. 1997;88:323-31.
31. Zhang X, Cao J, Jiang L, Geng C, Zhong L. Protective effect of hydroxytyrosol against acrylamide-induced cytotoxicity and DNA damage in HepG2 cells. Mutation research. 2009;664:64-8.
32. Boss V, Roback JD, Young AN, Roback LJ, Weisenhorn DM, Medina-Flores R, et al. Nerve growth factor, but not epidermal growth factor, increases Fra-2 expression and alters Fra-2/JunD binding to AP-1 and CREB binding elements in pheochromocytoma (PC12) cells. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2001;21:18-26.
33. Spencer JP, Vauzour D, Rendeiro C. Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects. Archives of biochemistry and biophysics. 2009;492:1-9.
34. Honda K, Shimohama S, Sawada H, Kihara T, Nakamizo T, Shibasaki H, et al. Nongenomic antiapoptotic signal transduction by estrogen in cultured cortical neurons. Journal of neuroscience research. 2001;64:466-75.
35. Leinninger GM, Backus C, Uhler MD, Lentz SI, Feldman EL. Phosphatidylinositol 3-kinase and Akt effectors mediate insulin-like growth factor-I neuroprotection in dorsal root ganglia neurons. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2004;18:1544-6.
36. Ng YP, Cheung ZH, Ip NY. STAT3 as a downstream mediator of Trk signaling and functions. The Journal of biological chemistry. 2006;281:15636-44.
37. Halliwell B. Oxidative stress and neurodegeneration: where are we now? Journal of neurochemistry. 2006;97:1634-58.
38. Jang JH, Surh YJ. Protective effects of resveratrol on hydrogen peroxide-induced apoptosis in rat pheochromocytoma (PC12) cells. Mutation research. 2001;496:181-90.
39. Rodriguez H, Holmquist GP, D'Agostino R, Jr., Keller J, Akman SA. Metal ion-dependent hydrogen peroxide-induced DNA damage is more sequence specific than metal specific. Cancer research. 1997;57:2394-403.
40. Mehri S, Abnous K, Mousavi SH, Shariaty VM, Hosseinzadeh H. Neuroprotective Effect of Crocin on Acrylamide-induced Cytotoxicity in PC12 cells. Cellular and Molecular Neurobiology. 2012;32:227-35.