TY - JOUR
T1 - The pleiotropic AMPK–CncC signaling pathway regulates the trade-off between detoxification and reproduction
AU - Jiang, Heng
AU - Meng, Xiangkun
AU - Zhang, Nan
AU - Ge, Huichen
AU - Wei, Jiaping
AU - Qian, Kun
AU - Zheng, Yang
AU - Park, Yoonseong
AU - Palli, Subba Reddy
AU - Wang, Jianjun
N1 - Publisher Copyright:
Copyright © 2023 the Author(s). Published by PNAS.
PY - 2023/3/7
Y1 - 2023/3/7
N2 - The association of decreased fecundity with insecticide resistance and the negative sublethal effects of insecticides on insect reproduction indicates the typical trade-off between two highly energy-demanding processes, detoxification and reproduction. However, the underlying mechanisms are poorly understood. The energy sensor adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Cap “n” collar isoform C (CncC) are important regulators of energy metabolism and xenobiotic response, respectively. In this study, using the beetle Tribolium castaneum as a model organism, we found that deltamethrin-induced oxidative stress activated AMPK, which promoted the nuclear translocation of CncC through its phosphorylation. The CncC not only acts as a transcription activator of cytochrome P450 genes but also regulates the expression of genes coding for ecdysteroid biosynthesis and juvenile hormone (JH) degradation enzymes, resulting in increased ecdysteroid levels as well as decreased JH titer and vitellogenin (Vg) gene expression. These data show that in response to xenobiotic stress, the pleiotropic AMPK–CncC signaling pathway mediates the trade-off between detoxification and reproduction by up-regulating detoxification genes and disturbing hormonal homeostasis.
AB - The association of decreased fecundity with insecticide resistance and the negative sublethal effects of insecticides on insect reproduction indicates the typical trade-off between two highly energy-demanding processes, detoxification and reproduction. However, the underlying mechanisms are poorly understood. The energy sensor adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Cap “n” collar isoform C (CncC) are important regulators of energy metabolism and xenobiotic response, respectively. In this study, using the beetle Tribolium castaneum as a model organism, we found that deltamethrin-induced oxidative stress activated AMPK, which promoted the nuclear translocation of CncC through its phosphorylation. The CncC not only acts as a transcription activator of cytochrome P450 genes but also regulates the expression of genes coding for ecdysteroid biosynthesis and juvenile hormone (JH) degradation enzymes, resulting in increased ecdysteroid levels as well as decreased JH titer and vitellogenin (Vg) gene expression. These data show that in response to xenobiotic stress, the pleiotropic AMPK–CncC signaling pathway mediates the trade-off between detoxification and reproduction by up-regulating detoxification genes and disturbing hormonal homeostasis.
KW - AMPK
KW - CncC
KW - detoxification
KW - reproduction
KW - xenobiotic stress
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U2 - 10.1073/pnas.2214038120
DO - 10.1073/pnas.2214038120
M3 - Article
C2 - 36853946
AN - SCOPUS:85149154595
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 10
M1 - e2214038120
ER -