Formaldehyde induces neurotoxicity to PC12 cells involving inhibition of paraoxonase-1 expression and activity.
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, H(2)S, 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.
Department of Physiology, Medical College, University of South China, Hengyang, Hunan, China. txq01001@gmail.com
Xiao-Qing
XQ
Tang
Yan-Kai
YK
Ren
Rong-Qian
RQ
Chen
Yuan-Yuan
YY
Zhuang
Heng-Rong
HR
Fang
Jin-Hua
JH
Xu
Chun-Yan
CY
Wang
Bi
B
Hu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D043303:Aryldialkylphosphatase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005557:Formaldehyde / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity*; D006862:Hydrogen Sulfide / Q000494:pharmacology; D006912:Hydroxyquinolines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D020258:Neurotoxicity Syndromes / Q000201:enzymology* / Q000209:etiology* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000201:enzymology / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
C494821:Bad protein, rat; D006912:Hydroxyquinolines; D017382:Reactive Oxygen Species; D051025:bcl-Associated Death Protein; D005557:Formaldehyde; C107724:2-hydroxyquinoline; D045304:Cytochromes c; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase; D006862:Hydrogen Sulfide