Aquatic Toxicology 181 (2016) 104–112 Contents lists available at ScienceDirect Aquatic Toxicology j o ur na l ho me pag e: www.elsevier.com/locate/aquatox Research paper BDE-47 induces oxidative stress, activates MAPK signaling pathway, and elevates de novo lipogenesis in the copepod Paracyclopina nana Min-Chul Lee a,1 , Jayesh Puthumana a,1 , Seung-Hwi Lee b,e,1 , Hye-Min Kang a , Jun Chul Park a , Chang-Bum Jeong a , Jeonghoon Han a , Dae-Sik Hwang a , Jung Soo Seo c , Heum Gi Park d , Ae-Son Om e,∗ , Jae-Seong Lee a,∗ a Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 16419, South Korea b Department of Food and Nutrition, College of Health Science, Honam University, Gwangju 62399, South Korea c Pathology Division, National Institute of Fisheries Science, Busan 46083, South Korea d Department of Marine Bioscience, College of Life Sciences, Gangneung-Wonju National University, Gangneung 25457, South Korea e Department of Food and Nutrition, College of Human Ecology, Hanyang University, Seoul 04763, South Korea a r t i c l e i n f o Article history: Received 5 October 2016 Received in revised form 21 October 2016 Accepted 24 October 2016 Available online 25 October 2016 Keywords: BDE-47 Paracyclopina nana Oxidative stress MAPK pathways DNL pathways Lipogenesis a b s t r a c t Brominated flame retardant, 2, 2  , 4, 4  -tetrabromodiphenyl ether (BDE-47), has received grave concerns as a persistent organic pollutant, which is toxic to marine organisms, and a suspected link to endocrine abnormalities. Despite the wide distribution in the marine ecosystem, very little is known about the toxic impairments on marine organisms, particularly on invertebrates. Thus, we examined the adverse effects of BDE-47 on life history trait (development), oxidative markers, fatty acid composition, and lipid accumulation in response to BDE-47-induced stress in the marine copepod Paracyclopina nana. Also, activation level of mitogen-activated protein kinase (MAPK) signaling pathways along with the gene expression profile of de novo lipogenesis (DNL) pathways were addressed. As a result, BDE-47 induced oxidative stress (e.g. reactive oxygen species, ROS) mediated activation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK) signaling cascades in MAPK pathways. Activated MAPK pathways, in turn, induced signal molecules that bind to the transcription factors (TFs) responsible for lipogenesis to EcR, SREBP, ChREBP promoters. Also, the stress stimulated the conversion of saturated fatty acids (SFAs) to polyunsaturated fatty acids (PUFAs), a preparedness of the organism to adapt the observed stress, which could be correlated with the elongase and desaturase gene (e.g. ELO3, 5-DES, 9- DES) expressions, and then extended to the delayed early post-embryonic development and increased accumulation of lipid droplets in P. nana. This study will provide a better understanding of how BDE-47 effects on marine invertebrates particularly on the copepods, an important link in the marine food chain. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Brominated flame retardants (BFRs) are a class of flame- retardant additives that have been extensively used in domestic and industrial materials to reduce their flammability (Lema et al., 2007; Díaz-Jaramillo et al., 2016). BFRs have been gained much attention due to low production cost and high efficiency, and poly- brominated diphenyl ethers (PBDEs) are the most widely used one ∗ Corresponding authors. E-mail addresses: aesonom@hanyang.ac.kr (A.-S. Om), jslee2@skku.edu (J.-S. Lee). 1 These authors equally contributed to this work. (Lema et al., 2007). Though the production of PBDEs has been banned in many countries, these compounds are considered as a new class of persistent organic pollutants (POPs) in the marine environments (Rahman et al., 2001; Yu et al., 2009; Bramwell et al., 2014). The congener of PBDEs, 2, 2  , 4, 4  -tetrabromodiphenyl ether (BDE-47) has elicited great concerns, as a chemical that is highly toxic to aquatic organisms and a suspected link to endocrine abnor- malities (Chan and Chan, 2012). Owing to their high lipophilicity and resistance to degradation, BDE-47 resulted in the worldwide distribution in all trophic levels through bioaccumulation and bio- transformation across the food web (Meng et al., 2007; USEPA, 2007; Nelson et al., 2015). With these properties, BDE-47 was detected as a dominant chemical in higher trophic level predators such as the porpoise Phocoena phocoena and the seabird Phalacro- http://dx.doi.org/10.1016/j.aquatox.2016.10.025 0166-445X/© 2016 Elsevier B.V. All rights reserved.