N-n-Butyl Haloperidol Iodide Ameliorates Oxidative Stress in Mitochondria Induced by HypoxiaReoxygenation through the Mitochondrial c-Jun N-Terminal KinaseSabSrcReactive Oxygen Species Pathway in H9c2 Cells

Joint Authors

Gao, Fenfei
Zhong, Shuping
Chu, Qianwen
Wang, Bin
Zhang, Zhaojing
Cai, Wenfeng
Zheng, Fuchun
Zhang, Yanmei
Shi, Ganggang
Li, Weiqiu
Chen, Yicun

Source

Oxidative Medicine and Cellular Longevity

Issue

Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-14, 14 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2019-05-08

Country of Publication

Egypt

No. of Pages

14

Main Subjects

Biology

Abstract EN

Both c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS) play important roles in myocardial ischemia/reperfusion (I/R) injury.

Our previous studies suggest that N-n-butyl haloperidol iodide (F2) exerts cardioprotection by reducing ROS production and JNK activation caused by I/R.

In this study, we hypothesized that there is a JNK/Sab/Src/ROS pathway in the mitochondria in H9c2 cells following hypoxia/reoxygenation (H/R) that induces oxidative stress in the mitochondria and that F2 exerts mitochondrial protective effects during H/R injury by modulating this pathway.

The results showed that H/R induced higher-level ROS in the cytoplasm on the one hand and JNK activation and translocation to the mitochondria by colocalization with Sab on the other.

Moreover, H/R resulted in mitochondrial Src dephosphorylation, and subsequently, oxidative stress evidenced by the increase in ROS generation and oxidized cardiolipin in the mitochondrial membranes and by the decrease in mitochondrial superoxide dismutase activity and membrane potential.

Furthermore, treatment with a JNK inhibitor or Sab small interfering RNA inhibited the mitochondrial translocation of p-JNK, decreased colocalization of p-JNK and Sab on the mitochondria, and reduced Src dephosphorylation and mitochondrial oxidative stress during H/R.

In addition, Src dephosphorylation by inhibitor PP2 increased mitochondrial ROS production.

F2, like inhibitors of the JNK/Sab/Src/ROS pathway, downregulated the H/R-induced mitochondrial translocation of p-JNK and the colocalization of p-JNK and Sab on the mitochondria, increased Src phosphorylation, and alleviated the above-mentioned mitochondrial oxidative stress.

In conclusion, F2 could ameliorate H/R-associated oxidative stress in mitochondria in H9c2 cells through the mitochondrial JNK/Sab/Src/ROS pathway.

American Psychological Association (APA)

Chu, Qianwen& Zhang, Yanmei& Zhong, Shuping& Gao, Fenfei& Chen, Yicun& Wang, Bin…[et al.]. 2019. N-n-Butyl Haloperidol Iodide Ameliorates Oxidative Stress in Mitochondria Induced by HypoxiaReoxygenation through the Mitochondrial c-Jun N-Terminal KinaseSabSrcReactive Oxygen Species Pathway in H9c2 Cells. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1205142

Modern Language Association (MLA)

Chu, Qianwen…[et al.]. N-n-Butyl Haloperidol Iodide Ameliorates Oxidative Stress in Mitochondria Induced by HypoxiaReoxygenation through the Mitochondrial c-Jun N-Terminal KinaseSabSrcReactive Oxygen Species Pathway in H9c2 Cells. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-14.
https://search.emarefa.net/detail/BIM-1205142

American Medical Association (AMA)

Chu, Qianwen& Zhang, Yanmei& Zhong, Shuping& Gao, Fenfei& Chen, Yicun& Wang, Bin…[et al.]. N-n-Butyl Haloperidol Iodide Ameliorates Oxidative Stress in Mitochondria Induced by HypoxiaReoxygenation through the Mitochondrial c-Jun N-Terminal KinaseSabSrcReactive Oxygen Species Pathway in H9c2 Cells. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1205142

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1205142