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Dysregulation of Sqstm1, mitophagy, and apoptotic genes in chronic exposure to arsenic and high-fat diet (HFD)

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Abstract

Arsenic (As) is a toxic and hazardous metalloid. Unfortunately, its presence in drinking water together with wrong nutritional patterns is associated with an increase in the occurrence of metabolic disorders in young people. Degradation of mitochondria is presented by a specific form of autophagy called mitophagy which is an important landmark leading to apoptosis during lipotoxicity. Lipotoxicity and cellular toxicity due to arsenic intake can lead to changes in mitophagy and apoptosis. The protein derived from SQSTM1 gene, also called p62, plays an important role in energy homeostasis in the liver, and it can contribute to the regulation of autophagic responses given its effect on signaling of mTOR, MAPK, and NF-KB. Consequently, changes in Sqstm1, mitophagy (BNIP3), and apoptotic (caspase 3) genes in the livers of NMRI mice were examined with the use of real-time RT-PCR Array followed by exposure to an environmentally relevant and negligible cytotoxic concentration of arsenite (50 ppm) in drinking water while being fed with a high-fat diet (HFD) or low-fat diet (LFD) for 20 weeks (LFD-As and HFD-As groups). While LFD-As and HFD groups showed a decrease in BNIP3 expression, a significant increase was observed in the HFD-As group. P62 gene showed downregulation in LFD-As and HFD groups, and upregeneration was observed in the HFD-As group. Caspase 3 showed increased expression as the key factor associated with apoptotic liver cell death in the three groups, with the highest value in HFD-As group. Overall, the changes observed in the expression of Sqstm1, BNIP3, and caspase 3 in this study can be related to the level of liver damage caused by exposure to arsenic and HFD and probably, BNIP3 pro-apoptotic protein is associated with an increased cell death due to HFD and As.

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Acknowledgements

This paper is issued from Ph.D. thesis of Marzieh Zeinvand-Lorestani.

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This paper was financially supported by Toxicology Research Center (Grant number TRC-9505) of Ahvaz Jundishapur University of Medical Sciences.

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Authors and Affiliations

  1. Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Marzieh Zeinvand-Lorestani, Heibatullah Kalantari & Mohammad Javad Khodayar

  2. Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Marzieh Zeinvand-Lorestani, Heibatullah Kalantari & Mohammad Javad Khodayar

  3. Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Ali Teimoori

  4. Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Najmaldin Saki & Fakher Rahim

  5. Health Research Institute, Diabetes Research Center, Department of Physiology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Akram Ahangarpour

  6. Cell and Molecular Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Layasadat Khorsandi

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  1. Marzieh Zeinvand-Lorestani
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  2. Heibatullah Kalantari
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Zeinvand-Lorestani, M., Kalantari, H., Khodayar, M.J. et al. Dysregulation of Sqstm1, mitophagy, and apoptotic genes in chronic exposure to arsenic and high-fat diet (HFD). Environ Sci Pollut Res 25, 34351–34359 (2018). https://doi.org/10.1007/s11356-018-3349-4

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