Blockade of Transient Receptor Potential Vanilloid 4 Enhances Antioxidation after Myocardial IschemiaReperfusion

Joint Authors

Du, Yimei
Wu, Qiongfeng
Lu, Kai
Zhao, Zhaoyang
Wang, Binbin
Liu, Huixia
Zhang, Shaoshao
Liao, Jie
Zeng, Yu
Dong, Qian
Zhao, Ning
Han, Bing

Source

Oxidative Medicine and Cellular Longevity

Issue

Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-17, 17 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2019-06-16

Country of Publication

Egypt

No. of Pages

17

Main Subjects

Biology

Abstract EN

Antioxidative stress provides a cardioprotective effect during myocardial ischemia/reperfusion (I/R).

Previous research has demonstrated that the blockade of transient receptor potential vanilloid 4 (TRPV4) attenuates myocardial I/R injury.

However, the underlying mechanism remains unclear.

The current study is aimed at investigating the antioxidative activity of TRPV4 inhibition and elucidating the underlying mechanisms in vitro and ex vivo.

We found that the inhibiting TRPV4 by the selective TRPV4 blocker HC-067047 or specific TRPV4-siRNA significantly reduces reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) levels in H9C2 cells exposed to hypoxia/reoxygenation (H/R).

Meanwhile, the activity of antioxidative enzymes, particularly superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), is enhanced.

Furthermore, after H/R, HC-067047 treatment increases the expression of P-Akt and the translocation of nuclear factor E2-related factor 2 (Nrf2) and related antioxidant response element (ARE) mainly including SOD, GSH-Px, and catalase (CAT).

LY294002, an Akt inhibitor, suppresses HC-067047 and specific TRPV4-siRNA-induced Nrf2 expression and its nuclear accumulation.

Nrf2 siRNA attenuates HC-067047 and specific TRPV4-siRNA-induced ARE expression.

In addition, treatment with LY294002 or Nrf2 siRNA significantly attenuates the antioxidant and anti-injury effects of HC-067047 in vitro.

Finally, in experiments on isolated rat hearts, we confirmed the antioxidative stress roles of TRPV4 inhibition during myocardial I/R and the application of exogenous H2O2.

In conclusion, the inhibition of TRPV4 exerts cardioprotective effects through enhancing antioxidative enzyme activity and expressions via the Akt/Nrf2/ARE pathway.

American Psychological Association (APA)

Wu, Qiongfeng& Lu, Kai& Zhao, Zhaoyang& Wang, Binbin& Liu, Huixia& Zhang, Shaoshao…[et al.]. 2019. Blockade of Transient Receptor Potential Vanilloid 4 Enhances Antioxidation after Myocardial IschemiaReperfusion. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1205090

Modern Language Association (MLA)

Wu, Qiongfeng…[et al.]. Blockade of Transient Receptor Potential Vanilloid 4 Enhances Antioxidation after Myocardial IschemiaReperfusion. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-17.
https://search.emarefa.net/detail/BIM-1205090

American Medical Association (AMA)

Wu, Qiongfeng& Lu, Kai& Zhao, Zhaoyang& Wang, Binbin& Liu, Huixia& Zhang, Shaoshao…[et al.]. Blockade of Transient Receptor Potential Vanilloid 4 Enhances Antioxidation after Myocardial IschemiaReperfusion. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1205090

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1205090