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Paraquat Induces Apoptosis through Cytochrome C Release and ERK Activation.

Seo HJ, Choi SJ, Lee JH - Biomol Ther (Seoul) (2014)

Bottom Line: Paraquat treatment resulted in activation of ERK, and U0126, inhibitors of the MEK/ERK signaling pathway, prevented apoptosis.Moreover, paraquat-induced apoptosis was associated with cytochrome C release, which could be prevented by treatment with the MEK inhibitors.Taken together, our findings suggest that ERK activation plays an active role in mediating paraquat-induced apoptosis of NIH3T3 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic and Cardiovascular Surgery, Chosun University School of Medicine, Gwangju 501-759, Republic of Korea.

ABSTRACT
Paraquat has been suggested to induce apoptosis by generation of reactive oxygen species (ROS). However, little is known about the mechanism of paraquat-induced apoptosis. Here, we demonstrate that extracellular signal-regulated protein kinase (ERK) is required for paraquat-induced apoptosis in NIH3T3 cells. Paraquat treatment resulted in activation of ERK, and U0126, inhibitors of the MEK/ERK signaling pathway, prevented apoptosis. Moreover, paraquat-induced apoptosis was associated with cytochrome C release, which could be prevented by treatment with the MEK inhibitors. Taken together, our findings suggest that ERK activation plays an active role in mediating paraquat-induced apoptosis of NIH3T3 cells.

No MeSH data available.


Related in: MedlinePlus

The effect of ROS on the activation of ERK1/2 induced by paraquat in NIH3T3 cells. (A) NIH3T3 cells were pretreated with different dose of NAC for 12 h and then treated with 1 mM paraquat. The extent of apoptosis was measured 24 h later. Results are shown as means ± S.D. (n=3). *<0.05. (B) Cells were treated with 1 mM paraquat for indicated time in the presence or absence of 5 mM NAC, and activity of ERK1/2 was determined as described in Fig. 2B.
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f6-bt-22-503: The effect of ROS on the activation of ERK1/2 induced by paraquat in NIH3T3 cells. (A) NIH3T3 cells were pretreated with different dose of NAC for 12 h and then treated with 1 mM paraquat. The extent of apoptosis was measured 24 h later. Results are shown as means ± S.D. (n=3). *<0.05. (B) Cells were treated with 1 mM paraquat for indicated time in the presence or absence of 5 mM NAC, and activity of ERK1/2 was determined as described in Fig. 2B.

Mentions: Recent evidence has suggested that ROS stimulate MAPK activities including ERK, p38 and JNK, which are key events in many cellular processes (Nikoletopoulou et al., 2013; Son et al., 2013). Therefore, intracellular ROS production by paraquat treatment was examined to determine whether or not it led to ERK activation, which could be involved in the paraquat-induced apoptosis. To test this possibility, the level of intracellular ROS production in response to paraquat was investigated using DCFHDA. We found that paraquat treatment led to significantly increase the intracellular ROS production, which could be completely blocked by treatment with 5 mM N-acetylcysteine (NAC) (data not shown). To further investigate the enhancement of ROS production by paraquat is involved in the induction of apoptosis, NIH3T3 cells were pretreated with NAC for 12 h. Subsequently, the cells were incubated with 1 mM of paraquat for an additional 24 h, and stained with propidium iodide, and the level of apoptosis was measured by FACsan flow cytometry. The data presented in Fig. 6A shows that NAC was able to significantly prevent paraquat-induced apoptosis, suggesting that intracellular ROS production is required for paraquat-induced apoptosis in NIH3T3 cells.


Paraquat Induces Apoptosis through Cytochrome C Release and ERK Activation.

Seo HJ, Choi SJ, Lee JH - Biomol Ther (Seoul) (2014)

The effect of ROS on the activation of ERK1/2 induced by paraquat in NIH3T3 cells. (A) NIH3T3 cells were pretreated with different dose of NAC for 12 h and then treated with 1 mM paraquat. The extent of apoptosis was measured 24 h later. Results are shown as means ± S.D. (n=3). *<0.05. (B) Cells were treated with 1 mM paraquat for indicated time in the presence or absence of 5 mM NAC, and activity of ERK1/2 was determined as described in Fig. 2B.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256029&req=5

f6-bt-22-503: The effect of ROS on the activation of ERK1/2 induced by paraquat in NIH3T3 cells. (A) NIH3T3 cells were pretreated with different dose of NAC for 12 h and then treated with 1 mM paraquat. The extent of apoptosis was measured 24 h later. Results are shown as means ± S.D. (n=3). *<0.05. (B) Cells were treated with 1 mM paraquat for indicated time in the presence or absence of 5 mM NAC, and activity of ERK1/2 was determined as described in Fig. 2B.
Mentions: Recent evidence has suggested that ROS stimulate MAPK activities including ERK, p38 and JNK, which are key events in many cellular processes (Nikoletopoulou et al., 2013; Son et al., 2013). Therefore, intracellular ROS production by paraquat treatment was examined to determine whether or not it led to ERK activation, which could be involved in the paraquat-induced apoptosis. To test this possibility, the level of intracellular ROS production in response to paraquat was investigated using DCFHDA. We found that paraquat treatment led to significantly increase the intracellular ROS production, which could be completely blocked by treatment with 5 mM N-acetylcysteine (NAC) (data not shown). To further investigate the enhancement of ROS production by paraquat is involved in the induction of apoptosis, NIH3T3 cells were pretreated with NAC for 12 h. Subsequently, the cells were incubated with 1 mM of paraquat for an additional 24 h, and stained with propidium iodide, and the level of apoptosis was measured by FACsan flow cytometry. The data presented in Fig. 6A shows that NAC was able to significantly prevent paraquat-induced apoptosis, suggesting that intracellular ROS production is required for paraquat-induced apoptosis in NIH3T3 cells.

Bottom Line: Paraquat treatment resulted in activation of ERK, and U0126, inhibitors of the MEK/ERK signaling pathway, prevented apoptosis.Moreover, paraquat-induced apoptosis was associated with cytochrome C release, which could be prevented by treatment with the MEK inhibitors.Taken together, our findings suggest that ERK activation plays an active role in mediating paraquat-induced apoptosis of NIH3T3 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic and Cardiovascular Surgery, Chosun University School of Medicine, Gwangju 501-759, Republic of Korea.

ABSTRACT
Paraquat has been suggested to induce apoptosis by generation of reactive oxygen species (ROS). However, little is known about the mechanism of paraquat-induced apoptosis. Here, we demonstrate that extracellular signal-regulated protein kinase (ERK) is required for paraquat-induced apoptosis in NIH3T3 cells. Paraquat treatment resulted in activation of ERK, and U0126, inhibitors of the MEK/ERK signaling pathway, prevented apoptosis. Moreover, paraquat-induced apoptosis was associated with cytochrome C release, which could be prevented by treatment with the MEK inhibitors. Taken together, our findings suggest that ERK activation plays an active role in mediating paraquat-induced apoptosis of NIH3T3 cells.

No MeSH data available.


Related in: MedlinePlus