X-Q Tang and Y-K Ren contributed equally to this work.
Formaldehyde induces neurotoxicity to PC12 cells involving inhibition of paraoxonase-1 expression and activity
Article first published online: 25 MAR 2011
© 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd
Clinical and Experimental Pharmacology and Physiology
Volume 38, Issue 4, pages 208–214, April 2011
How to Cite
Tang, X.-Q., Ren, Y.-K., Chen, R.-Q., Zhuang, Y.-Y., Fang, H.-R., Xu, J.-H., Wang, C.-Y. and Hu, B. (2011), Formaldehyde induces neurotoxicity to PC12 cells involving inhibition of paraoxonase-1 expression and activity. Clinical and Experimental Pharmacology and Physiology, 38: 208–214. doi: 10.1111/j.1440-1681.2011.05485.x
- Issue published online: 25 MAR 2011
- Article first published online: 25 MAR 2011
- Accepted manuscript online: 24 JAN 2011 11:38PM EST
- Received 15 August 2010; revision 1 January 2011; accepted 19 January 2011.
- cytochrome c;
- reactive oxygen species
1. Formaldehyde (FA) has been found to cause toxicity to neurons. However, its neurotoxic mechanisms have not yet been clarified. Increasing evidence has shown that oxidative damage is one of the most critical effects of formaldehyde exposure. Paraoxonase-1 (PON-1) is a pivotal endogenous anti-oxidant. Thus, we hypothesized that FA-mediated downregulation of PON1 is associated with its neurotoxicity.
2. In the present work, we used PC12 cells to study the neurotoxicity of FA and explore whether PON-1 is implicated in FA-induced neurotoxicity.
3. We found that FA has potent cytotoxic and apoptotic effects on PC12 cells. FA induces an accumulation of intracellular reactive oxygen species along with downregulation of Bcl-2 expression, as well as increased cytochrome c release. FA significantly suppressed the expression and activity of PON-1 in PC12 cells. Furthermore, H2S, an endogenous anti-oxidant gas, antagonizes FA-induced cytotoxicity as well as 2-hydroxyquinoline, a specific inhibitor of PON-1, which also induces cytotoxicity to PC12 cells.
4. The results of the present study provide, for the first time, evidence that the inhibitory effect on PON-1 expression and activity is involved in the neurotoxicity of FA, and suggest a promising role of PON-1 as a novel therapeutic strategy for FA-mediated toxicity.