PMID- 27576004
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20180104
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 309
DP  - 2016 Oct 15
TI  - AHR2 morpholino knockdown reduces the toxicity of total particulate matter to 
      zebrafish embryos.
PG  - 63-76
LID - S0041-008X(16)30247-2 [pii]
LID - 10.1016/j.taap.2016.08.024 [doi]
AB  - The zebrafish embryo has been proposed as a 'bridge model' to study the effects 
      of cigarette smoke on early development. Previous studies showed that exposure to 
      total particulate matter (TPM) led to adverse effects in developing zebrafish, 
      and suggested that the antioxidant and aryl hydrocarbon receptor (AHR) pathways 
      play important roles. This study investigated the roles of these two pathways in 
      mediating TPM toxicity. The study consisted of four experiments. In experiment I, 
      zebrafish embryos were exposed from 6h post fertilization (hpf) until 96hpf to 
      TPM0.5 and TPM1.0 (corresponding to 0.5 and 1.0mug/mL equi-nicotine units) in the 
      presence or absence of an antioxidant (N-acetyl cysteine/NAC) or a pro-oxidant 
      (buthionine sulfoximine/BSO). In experiment II, TPM exposures were performed in 
      embryos that were microinjected with nuclear factor erythroid 2-related factor 2 
      (Nrf2), AHR2, cytochrome P450 1A (CYP1A), or CYP1B1 morpholinos, and deformities 
      were assessed. In experiment III, embryos were exposed to TPM, and embryos/larvae 
      were collected at 24, 48, 72, and 96hpf to assess several genes associated with 
      the antioxidant and AHR pathways. Lastly, experiment IV assessed the activity and 
      protein levels of CYP1A and CYP1B1 after exposure to TPM. We demonstrate that the 
      incidence of TPM-induced deformities was generally not affected by NAC/BSO 
      treatments or Nrf2 knockdown. In contrast, AHR2 knockdown reduced, while CYP1A or 
      CYP1B1 knockdowns elevated the incidence of some deformities. Moreover, as shown 
      by gene expression the AHR pathway, but not the antioxidant pathway, was induced 
      in response to TPM exposure, providing further evidence for its importance in 
      mediating TPM toxicity.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Massarsky, Andrey
AU  - Massarsky A
AD  - Nicholas School of the Environment, Duke University, Durham, NC 27708, USA. 
      Electronic address: andrey.massarsky@duke.edu.
FAU - Bone, Audrey J
AU  - Bone AJ
AD  - Nicholas School of the Environment, Duke University, Durham, NC 27708, USA.
FAU - Dong, Wu
AU  - Dong W
AD  - Nicholas School of the Environment, Duke University, Durham, NC 27708, USA; 
      School of Animal Science and Technology, Inner Mongolia Provincial Key Laboratory 
      for Toxicants and Animal Disease, Inner Mongolia University for the 
      Nationalities, Tongliao, Inner Mongolia 028000, China.
FAU - Hinton, David E
AU  - Hinton DE
AD  - Nicholas School of the Environment, Duke University, Durham, NC 27708, USA.
FAU - Prasad, G L
AU  - Prasad GL
AD  - RAI Services Company, Winston-Salem, NC 27101, USA.
FAU - Di Giulio, Richard T
AU  - Di Giulio RT
AD  - Nicholas School of the Environment, Duke University, Durham, NC 27708, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160827
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Morpholinos)
RN  - 0 (Particulate Matter)
RN  - 0 (Receptors, Aryl Hydrocarbon)
SB  - IM
MH  - Animals
MH  - Embryo, Nonmammalian/*drug effects
MH  - Gene Knockdown Techniques
MH  - Morpholinos/*genetics
MH  - Particulate Matter/*toxicity
MH  - Receptors, Aryl Hydrocarbon/*genetics
MH  - Zebrafish/*embryology
OTO - NOTNLM
OT  - AHR pathway
OT  - Cigarette smoke
OT  - Oxidative stress
OT  - Total particulate matter (TPM)
OT  - Zebrafish development
EDAT- 2016/08/31 06:00
MHDA- 2017/06/07 06:00
CRDT- 2016/08/31 06:00
PHST- 2016/05/31 00:00 [received]
PHST- 2016/08/23 00:00 [revised]
PHST- 2016/08/25 00:00 [accepted]
PHST- 2016/08/31 06:00 [entrez]
PHST- 2016/08/31 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
AID - S0041-008X(16)30247-2 [pii]
AID - 10.1016/j.taap.2016.08.024 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2016 Oct 15;309:63-76. doi: 10.1016/j.taap.2016.08.024. 
      Epub 2016 Aug 27.