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Effect of N-n-butyl haloperidol iodide on ROS/JNK/Egr-1 signaling in H9c2 cells after hypoxia/reoxygenation.

Zhang Y, Liao H, Zhong S, Gao F, Chen Y, Huang Z, Lu S, Sun T, Wang B, Li W, Xu H, Zheng F, Shi G - Sci Rep (2015)

Bottom Line: The ROS scavengers edaravone (EDA) and N-acetyl-L-cysteine (NAC) reduced ROS level, downregulated JNK activation, and Egr-1 expression in H9c2 cells after H/R.The ROS donor hypoxanthine-xanthine oxidase (XO/HX) and the JNK activator ANISO antagonized the effects of F2.Therefore, H/R activates ROS/Egr-1 signaling pathway in H9c2 cells, and JNK activation plays an important role in this pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.

ABSTRACT
Reactive oxygen species (ROS)-induced oxidative stress in cells is an important pathophysiological process during myocardial ischemia/reperfusion (I/R) injury, and the transcription factor Egr-1 is a master switch for various damage pathways during reperfusion injury. An in vitro model of myocardial I/R injury and H9c2 cardiomyoblast cells hypoxia/reoxygenation (H/R) was used to assess whether there is abnormal intracellular ROS/JNK/Egr-1 signaling. We also assessed whether N-n-butyl haloperidol (F2), which exerts protective effects during myocardial I/R injury, can modulate this pathway. H/R induced ROS generation, JNK activation, and increased the expression of Egr-1 protein in H9c2 cells. The ROS scavengers edaravone (EDA) and N-acetyl-L-cysteine (NAC) reduced ROS level, downregulated JNK activation, and Egr-1 expression in H9c2 cells after H/R. The JNK inhibitor SP600125 inhibited Egr-1 overexpression in H9c2 cells caused by H/R. F2 could downregulate H/R-induced ROS level, JNK activation, and Egr-1 expression in H9c2 cells in a dose-dependent manner. The ROS donor hypoxanthine-xanthine oxidase (XO/HX) and the JNK activator ANISO antagonized the effects of F2. Therefore, H/R activates ROS/Egr-1 signaling pathway in H9c2 cells, and JNK activation plays an important role in this pathway. F2 regulates H/R-induced ROS/JNK/Egr-1 signaling, which might be an important mechanism by which it antagonizes myocardial I/R injury.

No MeSH data available.


Related in: MedlinePlus

Effects of a ROS donor, ROS scavengers, and a JNK inhibitor on the levels of total and p-JNK expression in H9c2 cells, as assessed using western blotting.A. Effects of a ROS donor; n = 6. B. Effects of ROS scavengers and a JNK inhibitor. n = 4. Cropped blots show protein levels of p-JNK, total JNK and β-actin. The bands were excised from different gels which were run under the same electrophoresis condition. Data are expressed as percentages of the control or H/R groups. All values are presented as mean ± S.E.M. *P < 0.05 vs. control; #P < 0.05 vs. H/R.
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f3: Effects of a ROS donor, ROS scavengers, and a JNK inhibitor on the levels of total and p-JNK expression in H9c2 cells, as assessed using western blotting.A. Effects of a ROS donor; n = 6. B. Effects of ROS scavengers and a JNK inhibitor. n = 4. Cropped blots show protein levels of p-JNK, total JNK and β-actin. The bands were excised from different gels which were run under the same electrophoresis condition. Data are expressed as percentages of the control or H/R groups. All values are presented as mean ± S.E.M. *P < 0.05 vs. control; #P < 0.05 vs. H/R.

Mentions: Compared with control, JNK activation was increased substantial in the XO/HX groups in a dose-dependent manner, whereas total JNK expression was unchanged (Fig. 3A). Conversely, JNK activation was decreased significantly in the presence of the ROS scavengers EDA (P = 0.027) and NAC (P < 0.001) and JNK inhibitor (P = 0.006), but total JNK expression was unchanged (Fig. 3B).


Effect of N-n-butyl haloperidol iodide on ROS/JNK/Egr-1 signaling in H9c2 cells after hypoxia/reoxygenation.

Zhang Y, Liao H, Zhong S, Gao F, Chen Y, Huang Z, Lu S, Sun T, Wang B, Li W, Xu H, Zheng F, Shi G - Sci Rep (2015)

Effects of a ROS donor, ROS scavengers, and a JNK inhibitor on the levels of total and p-JNK expression in H9c2 cells, as assessed using western blotting.A. Effects of a ROS donor; n = 6. B. Effects of ROS scavengers and a JNK inhibitor. n = 4. Cropped blots show protein levels of p-JNK, total JNK and β-actin. The bands were excised from different gels which were run under the same electrophoresis condition. Data are expressed as percentages of the control or H/R groups. All values are presented as mean ± S.E.M. *P < 0.05 vs. control; #P < 0.05 vs. H/R.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488875&req=5

f3: Effects of a ROS donor, ROS scavengers, and a JNK inhibitor on the levels of total and p-JNK expression in H9c2 cells, as assessed using western blotting.A. Effects of a ROS donor; n = 6. B. Effects of ROS scavengers and a JNK inhibitor. n = 4. Cropped blots show protein levels of p-JNK, total JNK and β-actin. The bands were excised from different gels which were run under the same electrophoresis condition. Data are expressed as percentages of the control or H/R groups. All values are presented as mean ± S.E.M. *P < 0.05 vs. control; #P < 0.05 vs. H/R.
Mentions: Compared with control, JNK activation was increased substantial in the XO/HX groups in a dose-dependent manner, whereas total JNK expression was unchanged (Fig. 3A). Conversely, JNK activation was decreased significantly in the presence of the ROS scavengers EDA (P = 0.027) and NAC (P < 0.001) and JNK inhibitor (P = 0.006), but total JNK expression was unchanged (Fig. 3B).

Bottom Line: The ROS scavengers edaravone (EDA) and N-acetyl-L-cysteine (NAC) reduced ROS level, downregulated JNK activation, and Egr-1 expression in H9c2 cells after H/R.The ROS donor hypoxanthine-xanthine oxidase (XO/HX) and the JNK activator ANISO antagonized the effects of F2.Therefore, H/R activates ROS/Egr-1 signaling pathway in H9c2 cells, and JNK activation plays an important role in this pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China.

ABSTRACT
Reactive oxygen species (ROS)-induced oxidative stress in cells is an important pathophysiological process during myocardial ischemia/reperfusion (I/R) injury, and the transcription factor Egr-1 is a master switch for various damage pathways during reperfusion injury. An in vitro model of myocardial I/R injury and H9c2 cardiomyoblast cells hypoxia/reoxygenation (H/R) was used to assess whether there is abnormal intracellular ROS/JNK/Egr-1 signaling. We also assessed whether N-n-butyl haloperidol (F2), which exerts protective effects during myocardial I/R injury, can modulate this pathway. H/R induced ROS generation, JNK activation, and increased the expression of Egr-1 protein in H9c2 cells. The ROS scavengers edaravone (EDA) and N-acetyl-L-cysteine (NAC) reduced ROS level, downregulated JNK activation, and Egr-1 expression in H9c2 cells after H/R. The JNK inhibitor SP600125 inhibited Egr-1 overexpression in H9c2 cells caused by H/R. F2 could downregulate H/R-induced ROS level, JNK activation, and Egr-1 expression in H9c2 cells in a dose-dependent manner. The ROS donor hypoxanthine-xanthine oxidase (XO/HX) and the JNK activator ANISO antagonized the effects of F2. Therefore, H/R activates ROS/Egr-1 signaling pathway in H9c2 cells, and JNK activation plays an important role in this pathway. F2 regulates H/R-induced ROS/JNK/Egr-1 signaling, which might be an important mechanism by which it antagonizes myocardial I/R injury.

No MeSH data available.


Related in: MedlinePlus