title: Vimentin-Mediated Steroidogenesis Induced by Phthalate Esters: Involvement of DNA Demethylation and Nuclear Factor κB.
abstract: Di-n-butyl phthalate (DBP) and its active metabolite, monobutyl phthalate (MBP) are the most common endocrine disrupting chemicals. Many studies indicate that high-doses of DBP and/or MBP exhibit toxicity on testicular function, however, little attention have been paid to the effects of low levels of DBP/MBP on steroidogenesis. As we all know, the steroidogenic acute regulatory protein (StAR) is a key regulator involved in the steroidogenesis. Here we found that, in addition to StAR, MBP/DBP increased the steroidogenesis by a cytoskeletal protein, vimentin. Briefly, in murine adrenocortical tumor (Y1) and the mouse Leydig tumor (MLTC-1) cells, vimentin regulated the secretion of progesterone. When these two cells were exposure to MBP, the DNA demethylation in the vimentin promoter was observed. In addition, MBP also induced the activation of nuclear factor kappa B (NF-κB, a transcriptional regulator of vimentin). These two processes improved the transcriptional elevation of vimentin. Knockdown of NF-κB/vimentin signaling blocked the DBP/MBP-induced steroidogenesis. These in vitro results were also confirmed via an in vivo model. By identifying a mechanism whereby DBP/MBP regulates vimentin, our results expand the understanding of the endocrine disrupting potential of phthalate esters.
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Hu
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Dong
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Lu
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hu
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Li
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Qin
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Yubang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D003993:Dibutyl Phthalate / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D052244:Endocrine Disruptors / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010795:Phthalic Acids / Q000737:chemistry / Q000633:toxicity; D011374:Progesterone / Q000097:blood / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D052244:Endocrine Disruptors; D016328:NF-kappa B; D010750:Phosphoproteins; D010795:Phthalic Acids; D014746:Vimentin; D000098682:Steroidogenic Acute Regulatory Protein; D003993:Dibutyl Phthalate; D011374:Progesterone; D004247:DNA; C028577:monobutyl phthalate