Carbofuran accelerates the cellular senescence and declines the life span of spns1 mutant zebrafish.

Alam Khan, Talukdar Mohammad Fahad, Tanjima Akther, Tanjeena Zaman, Md Faruk Hasan, Md Rafiqual Islam Khan, Mohammad Saiful Islam, Shuji Kishi

Journal of cellular and molecular medicine 2021 Jan

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Carbofuran is a carbamate pesticide, widely used in agricultural practices to increase crop productivity. In mammals, carbofuran is known to cause several untoward effects, such as apoptosis in the hippocampal neuron, oxidative stress, loss of memory and chromosomal anomalies. Most of these effects are implicated with cellular senescence. Therefore, the present study aimed to determine the effect of carbofuran on cellular senescence and biological ageing. Spinster homolog 1 (Spns1) is a transmembrane transporter, regulates autolysosomal biogenesis and plays a role in cellular senescence and survival. Using senescence-associated β-galactosidase staining, we found that carbofuran accelerates the cellular senescence in spns1 mutant zebrafish. The yolk opaqueness, a premature ageing phenotype in zebrafish embryos, was accelerated by carbofuran treatment. In the survival study, carbofuran shortened the life span of spns1 mutant zebrafish. Autophagy is the cellular lysosomal degradation, usually up-regulated in the senescent cells. To know the impact of carbofuran exposure on autophagy progress, we established a double-transgenic zebrafish line, harbouring EGFP-tagged LC3-II and mCherry-tagged Lamp1 on spns1 mutant background, whereas we found, carbofuran exposure synergistically accelerates autolysosome formation with insufficient lysosome-mediated degradation. Our data collectively suggest that carbofuran exposure synergistically accelerates the cellular senescence and affects biological ageing in spns1 defective animals. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Citation

Alam Khan, Talukdar Mohammad Fahad, Tanjima Akther, Tanjeena Zaman, Md Faruk Hasan, Md Rafiqual Islam Khan, Mohammad Saiful Islam, Shuji Kishi. Carbofuran accelerates the cellular senescence and declines the life span of spns1 mutant zebrafish. Journal of cellular and molecular medicine. 2021 Jan;25(2):1048-1059