TY - JOUR
T1 - Environmental carcinogen benzo[a]pyrene alters neutral lipid storage via a cyp-35A2 mediated pathway in Caenorhabditis elegans
AU - Chen, Yuzhi
AU - Abbass, Mustafa
AU - Brock, Trisha
AU - Hobbs, Gian
AU - Ciufo, Leonardo A.
AU - Hopkins, Christopher
AU - Arlt, Volker M.
AU - Stürzenbaum, Stephen R.
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/12/15
Y1 - 2023/12/15
N2 - Polycyclic aromatic hydrocarbons (PAHs), in particular benzo [a]pyrene (BaP), have been identified as carcinogenic components of tobacco smoke. In mammals, the toxicological response to BaP-diol-epoxide is driven by cytochrome P450 (CYP1A1), a pathway which is absent in Caenorhabditis elegans. In contrast, in worms prominently the CYP-35 enzyme family seems to be induced after BaP exposure. In C. elegans, BaP exposure reduces the accumulation of lysosomal neutral lipids in a dose dependent manner and the deletion of cyp-35A2 results in a significant elevation of neutral lipid metabolism. A cyp-35A2:mCherry;unc-47:GFP dual-labelled reporter strain facilitated the identification of three potential upstream regulators that drive BaP metabolism in worms, namely elt-2, nhr-49 and fos-1. This newly described reporter line is a powerful resource for future large-scale RNAi regarding toxicology and lipid metabolism screens.
AB - Polycyclic aromatic hydrocarbons (PAHs), in particular benzo [a]pyrene (BaP), have been identified as carcinogenic components of tobacco smoke. In mammals, the toxicological response to BaP-diol-epoxide is driven by cytochrome P450 (CYP1A1), a pathway which is absent in Caenorhabditis elegans. In contrast, in worms prominently the CYP-35 enzyme family seems to be induced after BaP exposure. In C. elegans, BaP exposure reduces the accumulation of lysosomal neutral lipids in a dose dependent manner and the deletion of cyp-35A2 results in a significant elevation of neutral lipid metabolism. A cyp-35A2:mCherry;unc-47:GFP dual-labelled reporter strain facilitated the identification of three potential upstream regulators that drive BaP metabolism in worms, namely elt-2, nhr-49 and fos-1. This newly described reporter line is a powerful resource for future large-scale RNAi regarding toxicology and lipid metabolism screens.
KW - Benzo[a]pyrene
KW - Caenorhabditis elegans
KW - Cyp-35A2
KW - Dual-labelled transgenic strain
KW - Lipid storage
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=85173992830&partnerID=8YFLogxK
U2 - 10.1016/j.envpol.2023.122731
DO - 10.1016/j.envpol.2023.122731
M3 - Article
C2 - 37839680
AN - SCOPUS:85173992830
SN - 0269-7491
VL - 339
JO - Environmental Pollution
JF - Environmental Pollution
M1 - 122731
ER -