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  3. Cell death induced by nicotine in human neuroblastoma SH-SY5Y cells is mainly attributed to cytoplasmic vacuolation originating from the trans-Golgi network

Cell death induced by nicotine in human neuroblastoma SH-SY5Y cells is mainly attributed to cytoplasmic vacuolation originating from the trans-Golgi network

  • Food Chem Toxicol. 2024 Jan 2:114431. doi: 10.1016/j.fct.2023.114431.
Jun Li 1,  Hongjuan Wang 2,  Huan Chen 2,  Xiao Li 2,  Yong Liu 3,  Hongwei Hou 4,  Qingyuan Hu 5
Affiliations

Affiliations

  • 1 Beijing Life Science Academy, Beijing, 100000, China; China National Tobacco Quality Supervision & Test Center, Zhengzhou, 450000, China; Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230000, China; University of Science and Technology of China, Hefei, 230000, China; Key Laboratory of Tobacco Biological Effects and Biosynthesis, Beijing, 100000, China; Key Laboratory of Tobacco Biological Effects, Zhengzhou, 450000, China.
  • 2 Beijing Life Science Academy, Beijing, 100000, China; China National Tobacco Quality Supervision & Test Center, Zhengzhou, 450000, China; Key Laboratory of Tobacco Biological Effects and Biosynthesis, Beijing, 100000, China; Key Laboratory of Tobacco Biological Effects, Zhengzhou, 450000, China.
  • 3 Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230000, China.
  • 4 Beijing Life Science Academy, Beijing, 100000, China; China National Tobacco Quality Supervision & Test Center, Zhengzhou, 450000, China; Key Laboratory of Tobacco Biological Effects and Biosynthesis, Beijing, 100000, China; Key Laboratory of Tobacco Biological Effects, Zhengzhou, 450000, China. Electronic address: [email protected].
  • 5 Beijing Life Science Academy, Beijing, 100000, China; China National Tobacco Quality Supervision & Test Center, Zhengzhou, 450000, China; Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230000, China; University of Science and Technology of China, Hefei, 230000, China; Key Laboratory of Tobacco Biological Effects and Biosynthesis, Beijing, 100000, China; Key Laboratory of Tobacco Biological Effects, Zhengzhou, 450000, China. Electronic address: [email protected].
PMID: 38176581 DOI: 10.1016/j.fct.2023.114431
Abstract

Humans are usually exposed to nicotine through the use of tobacco products. Although it is generally believed that nicotine is relatively harmless in tobacco consumption, it is, in fact, a toxic substance that warrants careful consideration of its potential toxicity. However, the current understanding of the neurotoxicity of nicotine is still very limited. In this study, we aim to reveal the toxic risk of nicotine to key target neuronal cells and its potential toxic mechanisms. The results showed that nicotine induced cell death, ROS increase, mitochondrial membrane potential decrease, and DNA damage in SH-SY5Y human neuroblastoma cells at millimolar concentrations, but did not cause toxic effects at the physiological concentration. These toxic effects were accompanied by cytoplasmic vacuolation. The inhibition of cytoplasmic vacuolation by bafilomycin A1 greatly reduced nicotine-induced cell death, indicating that cytoplasmic vacuolation is the key driving factor of cell death. These cytoplasmic vacuoles originated from the trans-Golgi network (TGN) and expressed microtubule-associated protein 1 LIGHT chain 3-II (LC3-II) and lysosomal associated membrane protein 1(LAMP1). The presence of LC3-II and LAMP1 within these vacuoles serves as evidence of compromised TGN structure and function. These findings provide valuable new insights into the potential neurotoxic risk and mechanisms of nicotine.

Keywords

Cell death; Cell vacuolation; Neurotoxicity; Nicotine; trans-Golgi network.

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