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Toxicology. 2014 Nov 5;325:67-73. doi: 10.1016/j.tox.2014.08.012. Epub 2014 Sep 2.

Lead induces COX-2 expression in glial cells in a NFAT-dependent, AP-1/NFκB-independent manner.

Author information

  • 1Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
  • 2Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA; Department of Occupational and Environmental Health and Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
  • 3Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 4Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
  • 5Department of Occupational and Environmental Health and Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
  • 6Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: jimingao@yahoo.com.
  • 7Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA. Electronic address: dongyun.zhang@nyumc.org.
  • 8Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA. Electronic address: chuanshu.huang@nyumc.org.

Abstract

Epidemiologic studies have provided solid evidence for the neurotoxic effect of lead for decades of years. In view of the fact that children are more vulnerable to the neurotoxicity of lead, lead exposure has been an urgent public health concern. The modes of action of lead neurotoxic effects include disturbance of neurotransmitter storage and release, damage of mitochondria, as well as induction of apoptosis in neurons, cerebrovascular endothelial cells, astroglia and oligodendroglia. Our studies here, from a novel point of view, demonstrates that lead specifically caused induction of COX-2, a well known inflammatory mediator in neurons and glia cells. Furthermore, we revealed that COX-2 was induced by lead in a transcription-dependent manner, which relayed on transcription factor NFAT, rather than AP-1 and NFκB, in glial cells. Considering the important functions of COX-2 in mediation of inflammation reaction and oxidative stress, our studies here provide a mechanistic insight into the understanding of lead-associated inflammatory neurotoxicity effect via activation of pro-inflammatory NFAT3/COX-2 axis.

KEYWORDS:

COX-2; Lead; NFAT; Neurotoxicity

PMID:
25193092
PMCID:
PMC4238429
DOI:
10.1016/j.tox.2014.08.012
[PubMed - indexed for MEDLINE]
Free PMC Article
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