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N-acetylcysteine alleviated paraquat-induced mitochondrial fragmentation and autophagy in primary murine neural progenitor cells.
J Appl Toxicol. 2019 11; 39(11):1557-1567.JA

Abstract

The developing brain is uniquely vulnerable to toxic chemical exposures. Studies indicate that neural stem cell (NSC) self-renewal is susceptible to oxidative stress caused by xenobiotics. However, the impact of antioxidants on NSC self-renewal and the potential mechanisms remain elusive. In this study, primary murine neural progenitor cells (mNPCs) from the subventricular zone were used as a research model. In addition, paraquat (PQ) was used to elicit oxidative stress and N-acetylcysteine (NAC) was used as a powerful antioxidant. mNPCs were treated with 80 μm PQ for 24 hours with or without 4 hours of NAC pretreatment. Our results showed that PQ treatment increased intracellular reactive oxygen species production, decreased cell viability and DNA synthesis, and promoted cell apoptosis. Meanwhile, pretreatment with NAC alleviated PQ-induced cytotoxicity in mNPCs. To elucidate the mechanisms further, we found that NAC pretreatment prevented PQ-induced reactive oxygen species production, mitochondrial fragmentation and autophagy in mNPCs. NAC-pretreated cells showed increased anti-apoptotic protein Bcl-2 and decreased pro-apoptotic protein Bax expression. Similarly, NAC pretreatment increased p-mTOR and decreased LC3B-II protein expression. Moreover, NAC decreased mitophagy related mRNA Pink1 and Parkin expression. Taken together, our results suggested that the antioxidant NAC treatment significantly attenuated PQ-induced mNPC self-renewal disruption through decreasing autophagy and salvaging mitochondrial morphology. These findings revealed a potential mechanism for neurological treatment relating to antioxidant and suggested potentially relevant implications for PQ-related neurodegenerative disorders. Thus, our study also provided insight into therapeutic strategies for the neurotoxic effects of oxidative stress-associated toxicants.

Authors+Show Affiliations

School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China. The Department of Science and Research, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31368586

Citation

Xiong, Guiya, et al. "N-acetylcysteine Alleviated Paraquat-induced Mitochondrial Fragmentation and Autophagy in Primary Murine Neural Progenitor Cells." Journal of Applied Toxicology : JAT, vol. 39, no. 11, 2019, pp. 1557-1567.
Xiong G, Zhao L, Yan M, et al. N-acetylcysteine alleviated paraquat-induced mitochondrial fragmentation and autophagy in primary murine neural progenitor cells. J Appl Toxicol. 2019;39(11):1557-1567.
Xiong, G., Zhao, L., Yan, M., Wang, X., Zhou, Z., & Chang, X. (2019). N-acetylcysteine alleviated paraquat-induced mitochondrial fragmentation and autophagy in primary murine neural progenitor cells. Journal of Applied Toxicology : JAT, 39(11), 1557-1567. https://doi.org/10.1002/jat.3839
Xiong G, et al. N-acetylcysteine Alleviated Paraquat-induced Mitochondrial Fragmentation and Autophagy in Primary Murine Neural Progenitor Cells. J Appl Toxicol. 2019;39(11):1557-1567. PubMed PMID: 31368586.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - N-acetylcysteine alleviated paraquat-induced mitochondrial fragmentation and autophagy in primary murine neural progenitor cells. AU - Xiong,Guiya, AU - Zhao,Lina, AU - Yan,Mengling, AU - Wang,Xinjin, AU - Zhou,Zhijun, AU - Chang,Xiuli, Y1 - 2019/08/01/ PY - 2019/03/10/received PY - 2019/05/21/revised PY - 2019/06/03/accepted PY - 2019/8/2/pubmed PY - 2020/10/8/medline PY - 2019/8/2/entrez KW - N-acetylcysteine KW - apoptosis KW - autophagy KW - mitochondrial morphology KW - neural progenitor cells KW - paraquat SP - 1557 EP - 1567 JF - Journal of applied toxicology : JAT JO - J Appl Toxicol VL - 39 IS - 11 N2 - The developing brain is uniquely vulnerable to toxic chemical exposures. Studies indicate that neural stem cell (NSC) self-renewal is susceptible to oxidative stress caused by xenobiotics. However, the impact of antioxidants on NSC self-renewal and the potential mechanisms remain elusive. In this study, primary murine neural progenitor cells (mNPCs) from the subventricular zone were used as a research model. In addition, paraquat (PQ) was used to elicit oxidative stress and N-acetylcysteine (NAC) was used as a powerful antioxidant. mNPCs were treated with 80 μm PQ for 24 hours with or without 4 hours of NAC pretreatment. Our results showed that PQ treatment increased intracellular reactive oxygen species production, decreased cell viability and DNA synthesis, and promoted cell apoptosis. Meanwhile, pretreatment with NAC alleviated PQ-induced cytotoxicity in mNPCs. To elucidate the mechanisms further, we found that NAC pretreatment prevented PQ-induced reactive oxygen species production, mitochondrial fragmentation and autophagy in mNPCs. NAC-pretreated cells showed increased anti-apoptotic protein Bcl-2 and decreased pro-apoptotic protein Bax expression. Similarly, NAC pretreatment increased p-mTOR and decreased LC3B-II protein expression. Moreover, NAC decreased mitophagy related mRNA Pink1 and Parkin expression. Taken together, our results suggested that the antioxidant NAC treatment significantly attenuated PQ-induced mNPC self-renewal disruption through decreasing autophagy and salvaging mitochondrial morphology. These findings revealed a potential mechanism for neurological treatment relating to antioxidant and suggested potentially relevant implications for PQ-related neurodegenerative disorders. Thus, our study also provided insight into therapeutic strategies for the neurotoxic effects of oxidative stress-associated toxicants. SN - 1099-1263 UR - https://www.unboundmedicine.com/medline/citation/31368586/N_acetylcysteine_alleviated_paraquat_induced_mitochondrial_fragmentation_and_autophagy_in_primary_murine_neural_progenitor_cells_ L2 - https://doi.org/10.1002/jat.3839 DB - PRIME DP - Unbound Medicine ER -