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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.


Inhibition of induction of apoptosis in NIH3T3 cells exposed to paraquat after pretreatment with the MEK inhibitor, U0126. Left panel, percentage of apoptotic cells was shown using PI staining. Results are shown as means ± S.D. (n=3). *<0.05. Right panel, inhibition of ERK1/2 activation by 20 μM U0126 was determined as described in Fig. 2B.
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f3-bt-22-503: Inhibition of induction of apoptosis in NIH3T3 cells exposed to paraquat after pretreatment with the MEK inhibitor, U0126. Left panel, percentage of apoptotic cells was shown using PI staining. Results are shown as means ± S.D. (n=3). *<0.05. Right panel, inhibition of ERK1/2 activation by 20 μM U0126 was determined as described in Fig. 2B.

Mentions: To evaluate the functional consequence of ERK activation in paraquat-induced apoptosis, we used commercially available MEK1/2 inhibitory compound U0126, which are highly selective in its inhibition of ERK pathway. We observed that pretreatment of NIH3T3 cells with 20 μM U0126 totally abolished ERK phosphorylation in response to paraquat treatment (Fig. 3, right panel). Paraquat-induced apoptosis was significantly reduced when cells were pretreated with U0126 for 30 min prior to addition of 1 mM paraquat, and this protective effect of the MEK inhibitors was dose-dependent and occurred with doses expected to suppress ERK activation (Fig. 3, left panel).


Paraquat Induces Apoptosis through Cytochrome C Release and ERK Activation.

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

Inhibition of induction of apoptosis in NIH3T3 cells exposed to paraquat after pretreatment with the MEK inhibitor, U0126. Left panel, percentage of apoptotic cells was shown using PI staining. Results are shown as means ± S.D. (n=3). *<0.05. Right panel, inhibition of ERK1/2 activation by 20 μM U0126 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

f3-bt-22-503: Inhibition of induction of apoptosis in NIH3T3 cells exposed to paraquat after pretreatment with the MEK inhibitor, U0126. Left panel, percentage of apoptotic cells was shown using PI staining. Results are shown as means ± S.D. (n=3). *<0.05. Right panel, inhibition of ERK1/2 activation by 20 μM U0126 was determined as described in Fig. 2B.
Mentions: To evaluate the functional consequence of ERK activation in paraquat-induced apoptosis, we used commercially available MEK1/2 inhibitory compound U0126, which are highly selective in its inhibition of ERK pathway. We observed that pretreatment of NIH3T3 cells with 20 μM U0126 totally abolished ERK phosphorylation in response to paraquat treatment (Fig. 3, right panel). Paraquat-induced apoptosis was significantly reduced when cells were pretreated with U0126 for 30 min prior to addition of 1 mM paraquat, and this protective effect of the MEK inhibitors was dose-dependent and occurred with doses expected to suppress ERK activation (Fig. 3, left panel).

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.