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JNK and p38 MAPK regulate oxidative stress and the inflammatory response in chlorpyrifos-induced apoptosis

Yeo-Woon Ki1, Jae Hyeon Park, Jeong Eun Lee

  • 1Department of Pharmacology, College of Medicine, Hanyang University, 133-791 Seoul, Republic of Korea.

Toxicology Letters
|February 19, 2013
PubMed

Insights

Chlorpyrifos pesticide induces neuronal cell death by increasing reactive oxygen species (ROS) and activating JNK/p38 MAPK pathways. These pathways are crucial for CPF-induced apoptosis and inflammation via ROS and COX-2.

Area of Science:

  • Neuroscience
  • Toxicology
  • Cell Biology

Background:

  • Chlorpyrifos (CPF) is a widely used pesticide with known neurotoxic effects.
  • Understanding the precise mechanisms of CPF-induced neuronal cell death is critical for public health.
  • Reactive oxygen species (ROS) and cyclooxygenase-2 (COX-2) are implicated in neuronal damage.

Purpose of the Study:

  • To investigate the role of ROS and COX-2 in chlorpyrifos-induced neuronal cell death.
  • To elucidate the involvement of MAPK pathways in CPF neurotoxicity.
  • To determine the specific MAPK pathways mediating apoptosis and inflammation.

Main Methods:

  • Human neuroblastoma SH-SY5Y cells were treated with chlorpyrifos (CPF).
  • Levels of ROS and expression of COX-2 were measured.
  • MAPK pathways (JNK, ERK1/2, p38 MAPK) were analyzed.
  • The effects of MAPK inhibitors on cytotoxicity, ROS generation, and COX-2 expression were evaluated.

Main Results:

  • CPF treatment led to increased ROS production and cytotoxicity in SH-SY5Y cells.
  • CPF activated JNK, ERK1/2, and p38 MAPK pathways.
  • MAPK inhibitors reduced CPF-induced cytotoxicity and ROS generation.
  • CPF treatment upregulated COX-2 expression, which was attenuated by JNK and p38 MAPK inhibitors, but not ERK1/2 inhibitors.

Conclusions:

  • CPF induces neuronal apoptosis through ROS production and MAPK activation.
  • The JNK and p38 MAPK pathways are critical mediators of CPF-induced neuronal apoptosis.
  • JNK and p38 MAPK pathways are involved in the inflammatory response by up-regulating COX-2.

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