کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5561747 | 1562285 | 2017 | 53 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
PPARα-independent transcriptional targets of perfluoroalkyl acids revealed by transcript profiling
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کلمات کلیدی
perfluorohexanesulfonic acidLXRERαPFHxSnuclear factor erythroid-2-related factor 2DEHPEREPPARαPFAAsPPARγNrf2PFNAPFUnDAPFOSPFOAAHRdi-(2-ethylhexyl)phthalate - di- (2-اتیل هگزیل) فتالاتPerfluorononanoic acid - اسید PerfluorononanoicPerfluoroalkyl acids - اسیدهای PerfluoroalkylPerfluorooctane sulfonate - سولفونات Perfluorooctaneestrogen response element - عنصر پاسخ استروژنCAR - ماشینGrowth hormone - هورمون رشدPerfluorooctanoic acid - پرفلوئورواکتانوئیک اسیدliver X receptor - کبد X گیرندهaryl hydrocarbon receptor - گیرنده آرویل هیدروکربنEstrogen receptor α - گیرنده استروژن αperoxisome proliferator-activated receptor γ - گیرنده پروتئین کننده پروکسیوم فعال γperoxisome proliferator-activated receptor α - گیرنده پروتئینی فعال پروکسایزوم α
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Perfluoroalkyl acids (PFAAs) are ubiquitous and persistent environmental contaminants. Compounds such as perfluoroocanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) are readily found in the tissues of humans and wildlife. While PFOA and PFOS have been the subject of numerous studies since they were first described over a decade ago, less is known about the biological activity of PFHxS and PFNA. Most PFAAs are activators of peroxisome proliferator-activated receptor α (PPARα), although the biological effects of these compounds are likely mediated by other factors in addition to PPARα. To evaluate the effects of PFHxS and PFNA, male wild-type and Pparα-null mice were dosed by oral gavage with PFHxS (3 or 10 mg/kg/day), PFNA (1 or 3 mg/kg/day), or vehicle for 7 days, and liver gene expression was evaluated by full-genome microarrays. Gene expression patterns were then compared to historical in-house data for PFOA and PFOS in addition to the experimental hypolipidemic agent, WY-14,643. While WY-14,643 altered most genes in a PPARα-dependent manner, approximately 11-24% of regulated genes in PFAA-treated mice were independent of PPARα. The possibility that PFAAs regulate gene expression through other molecular pathways was evaluated. Using data available through a microarray database, PFAA gene expression profiles were found to exhibit significant similarity to profiles from mouse tissues exposed to agonists of the constitutive activated receptor (CAR), estrogen receptor α (ERα), and PPARγ. Human PPARγ and ERα were activated by all four PFAAs in trans-activation assays from the ToxCast screening program. Predictive gene expression biomarkers showed that PFAAs activate CAR in both genotypes and cause feminization of the liver transcriptome through suppression of signal transducer and activator of transcription 5 B (STAT5B). These results indicate that, in addition to activating PPARα as a primary target, PFAAs also have the potential to activate CAR, PPARγ, and ERα as well as suppress STAT5B.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 387, 15 July 2017, Pages 95-107
Journal: Toxicology - Volume 387, 15 July 2017, Pages 95-107
نویسندگان
Mitchell B. Rosen, Kaberi P. Das, John Rooney, Barbara Abbott, Christopher Lau, J. Christopher Corton,