1. Academic Validation
  2. Effect of lower chlorinated hydroxylated-polychlorobiphenyls on development of PC12 cells

Effect of lower chlorinated hydroxylated-polychlorobiphenyls on development of PC12 cells

  • Environ Sci Pollut Res Int. 2018 Jun;25(17):16434-16445. doi: 10.1007/s11356-017-9604-2.
Satomi Mizukami-Murata 1 2 Katsuhide Fujita 3 Takeshi Nakano 4
Affiliations

Affiliations

  • 1 Public Works Research Institute (PWRI), PWRI, 3-1-3 Minamiyama, Tsukuba, Ibaraki, Japan. s-murata@pwri.go.jp.
  • 2 The Japan Society for the Promotion of Science (JSPS), and National Institute for Agro-Environmental Sciences (NIAES), Tsukuba, Japan. s-murata@pwri.go.jp.
  • 3 National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
  • 4 Osaka University, Suita, Osaka, Japan.
Abstract

Hydroxylated polychlorobiphenyls (OH-PCBs) are major metabolites of PCBs that are widely distributed in the environment. While the effects of penta- to hepta-chlorinated OH-PCBs on neuronal differentiation have been widely reported, those of lower chlorinated OH-PCBs have not been extensively studied. To investigate the effects of lower chlorinated OH-PCBs on neuronal development, we studied the effects of mono- to hexa-chlorinated OH-PCBs on PC12 cells. Morphological changes were examined using an automatic system IN Cell Analyzer. Seventeen of the 20 OH-PCBs investigated promoted neuronal elongation in an OH-PCB concentration-dependent manner, while three OH-PCB congeners suppressed neuronal elongation based on Dunnett's analysis. In particular, the top five OH-PCBs (4OH-PCB2, 4'OH-PCB3, 4'OH-PCB25, 4'OH-PCB68, and 4'OH-PCB159), which have hydroxyl groups at the para-position and chlorine substitutions at the 2, 4, or 3' positions, significantly promoted neuronal elongation. Moreover, these neuronal elongations were suppressed by U0126, and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was observed in PC12 cells treated with 4OH-PCB2, 4'OH-PCB25, and 4'OH-PCB159. Taken together, our results indicate that the effect of OH-PCB on neuronal development is not dependent on the number of chlorine groups but on the chemical structure, and the mitogen-activated kinase kinase (MEK)-ERK1/2 signaling pathway is involved in this process.

Keywords

Lower chlorinated OH-PCBs; MEK-ERK1/2 signaling pathway; Neuronal development; PC12 cells.

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