The mechanistic target of rapamycin (RAPA) complex 1 (mTORC1) - transcription factor EB (TFEB) pathway plays a crucial role in response to nutritional status, energy and environmental stress for maintaining cellular homeostasis. But there is few reports on its role in the toxic effects of arsenic exposure and the related mechanisms. Here, we show that the exposure of bronchial epithelial cells (BEAS-2B) to sodium arsenite promoted the activation of mTORC1 (p-mTORC1) and the inactivation of TFEB (p-TFEB), the number and activity of lysosomes decreased, the content of reduced glutathione (GSH) and superoxide dismutase (SOD) decreased, the content of malondialdehyde (MDA) increased, the DNA and chromosome damage elevated. Further, when mTORC1 was inhibited with RAPA, p-mTORC1 and p-TFEB down-regulated, GSH and SOD increased, MDA decreased, the DNA and chromosome damage reduced significantly, as compared with the control group. Our data revealed for the first time that mTORC1 - TFEB pathway was involved in sodium arsenite induced lysosomal alteration, oxidative stress and genetic damage in BEAS-2B cells, and it may be a potential intervention target for the toxic effects of arsenic.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.tox.2024.153795 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Actions of dexmedetomidine in regulating NLRP3 in postoperative cognitive dysfunction in aged mice via the autophagy-lysosome pathway.
Br J Pharmacol
January 2025
Institute of Neurobiology, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Background And Purpose: Autophagy-lysosomal pathway dysfunction leads to postoperative cognitive dysfunction (POCD). Dexmedetomidine (Dex) improves POCD, and we probed the effects of Dex on autophagy-lysosomal pathway dysfunction in a POCD model.
Experimental Approach: A POCD mouse model was established and intraperitoneally injected with Dex.
Tianxiangdan suppresses foam cell formation by enhancing lipophagy and reduces the progression of atherosclerosis.
In Vitro Cell Dev Biol Anim
January 2025
College of Traditional Chinese Medicine, Xinjiang Uygur Autonomous Region, Xinjiang Medical University, Urumqi, 830063, China.
The aim of this study is to assess the impact of Tianxiangdan (TXD) on lipophagy in foam cells and its underlying mechanism in treating atherosclerosis, particularly focusing on its efficacy in lowering blood lipids. In vivo, ApoE-/- atherosclerosis mouse models were established for group intervention. Blood lipid levels of the mice were measured, lipid deposition and autophagy levels in atherosclerotic plaques were assessed, and co-localization of lipid droplets and autophagosomes was examined.
View Article and Find Full Text PDFUpregulated astrocyte HDAC7 induces Alzheimer-like tau pathologies via deacetylating transcription factor-EB and inhibiting lysosome biogenesis.
Mol Neurodegener
January 2025
College of Life Sciences and Oceanography, Brain Disease and Big Data Research Institute, Shenzhen University, Shenzhen, 518060, Guangdong, China.
Background: Astrocytes, the most abundant glial cell type in the brain, will convert into the reactive state in response to proteotoxic stress such as tau accumulation, a characteristic feature of Alzheimer's disease (AD) and other tauopathies. The formation of reactive astrocytes is partially attributed to the disruption of autophagy lysosomal signaling, and inhibiting of some histone deacetylases (HDACs) has been demonstrated to reduce the molecular and functional characteristics of reactive astrocytes. However, the precise role of autophagy lysosomal signaling in astrocytes that regulates tau pathology remains unclear.
View Article and Find Full Text PDFActivation of TFEB protects against diabetic vascular calcification by improving autophagic flux and activating Nrf2 antioxidant system.
Am J Physiol Endocrinol Metab
January 2025
Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University 87 Dingjiaqiao, Nanjing, P.R. China.
Autophagic flux blockade and excessive oxidative stress play important roles in the pathogenesis of diabetic vascular calcification (VC). Transcription factor EB (TFEB) is an important regulator of many autophagy-lysosomal related components, which is mainly involved in promoting autophagy process in cells. Nuclear factor erythroid-2 related factor 2 (Nrf2) antioxidant system is considered as one of the key pathways in response to intracellular oxidative stress.
View Article and Find Full Text PDFFangchinoline eliminates intracellular Salmonella by enhancing lysosomal function via the AMPK-mTORC1-TFEB axis.
J Adv Res
January 2025
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, China; Institute of Comparative Medicine, Yangzhou University, Yangzhou, China. Electronic address:
Introduction: Salmonella, a foodborne zoonotic pathogen, is a significant cause of morbidity and mortality in animals and humans globally. With the prevalence of multidrug-resistant strains, Salmonellosis has become a formidable challenge. Host-directed therapy (HDT) has recently emerged as a promising anti-infective approach for treating intracellular bacterial infections.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!