دورية أكاديمية
أعرض في EDS

Exposure to microcystin-LR promotes astrocyte proliferation both in vitro and in vivo via Hippo signaling pathway.

التفاصيل البيبلوغرافية
العنوان: Exposure to microcystin-LR promotes astrocyte proliferation both in vitro and in vivo via Hippo signaling pathway.
المؤلفون: Xue Q; State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, PR China., Yan Y; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China., Zhang K; State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, PR China., Zhang H; State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, PR China., Zhao Y; State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, PR China. Electronic address: yyzhao@niglas.ac.cn.
المصدر: Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2024 Jul 01; Vol. 279, pp. 116480. Date of Electronic Publication: 2024 May 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7805381 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2414 (Electronic) Linking ISSN: 01476513 NLM ISO Abbreviation: Ecotoxicol Environ Saf Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam, Netherlands : Elsevier
مواضيع طبية MeSH: Microcystins*/toxicity , Astrocytes*/drug effects , Marine Toxins* , Hippo Signaling Pathway*/drug effects , Signal Transduction*/drug effects , Cell Proliferation*/drug effects, Animals ; Mice ; Protein Serine-Threonine Kinases/metabolism ; Protein Serine-Threonine Kinases/genetics ; YAP-Signaling Proteins ; Cell Survival/drug effects ; Transcription Factors/metabolism ; Transcription Factors/genetics ; ErbB Receptors/metabolism ; TEA Domain Transcription Factors ; DNA-Binding Proteins/metabolism ; DNA-Binding Proteins/genetics
مستخلص: Microcystins (MCs) are toxic to the central nervous system of mammals. However, the direct toxicity of MCs on mammalian brain cells and the involved molecular mechanisms are not fully elucidated. Here, we incubated primary astrocytes, the major glial cell-type in the brain, with 0-12.5 μM concentrations of MC-LR for 48 h, and the impairment was evaluated. We found that MC-LR caused significant increases in the cell viability at the range of 0.05-1 μM concentrations with the highest density at 0.1 μM concentration. Treatment with 0.1 μM MC-LR induced YAP nuclear translocation and decreased the ratio of p-YAP to YAP. It also decreased mRNA levels of the upstream regulator (AMOT), and enhanced expressions of YAP interacted genes (Egfr, Tead1, and Ctgf) in primary astrocytes. Overexpression of AMOT significantly attenuated the increase of MC-LR-induced astrocyte proliferation and the expression of YAP downstream genes. These results indicate that Hippo signaling contributed to MC-LR-caused astrocyte proliferation. Further, reactive astrogliosis was observed in the mice brain after MC-LR exposure to environmentally relevant concentrations (20 or 100 μg/L) through drinking water for 16 weeks. Pathological observations revealed that 100 μg/L MC-LR exposure caused neuronal damages with characteristics of shrunken or vacuolation in the region of the cerebral cortex, striatum and cerebellum. These results were accompanied with increased oxidative stress and inflammatory response. Our data reveal the potential astrocytic mechanisms in MC-induced neurotoxicity and raise an alarm for neurodegenerative disease risk following daily exposure to MC-LR.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Cell proliferation; Hippo signaling pathway; Microcystin; Primary astrocytes; Reactive astrogliosis
المشرفين على المادة: 0 (Microcystins)
EQ8332842Y (cyanoginosin LR)
0 (Marine Toxins)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
0 (YAP-Signaling Proteins)
0 (Yap1 protein, mouse)
0 (Transcription Factors)
0 (Tead1 protein, mouse)
EC 2.7.10.1 (ErbB Receptors)
0 (TEA Domain Transcription Factors)
EC 2.7.10.1 (EGFR protein, mouse)
0 (DNA-Binding Proteins)
تواريخ الأحداث: Date Created: 20240521 Date Completed: 20240606 Latest Revision: 20240606
رمز التحديث: 20240607
DOI: 10.1016/j.ecoenv.2024.116480
PMID: 38772146
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2414
DOI:10.1016/j.ecoenv.2024.116480