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Src-IL-18 signaling regulates the secretion of atrial natriuretic factor in hypoxic beating rat atria

Xiang Li, Cheng-xi Wei, Cheng-zhe Wu, Lan Hong, Zhuo-na Han, Ying Liu, Wang Yue-ying, Xun Cui
DOI: 10.33963/KP.a2021.0051
·
Pubmed: 34176112

open access

Online first
Original article
Published online: 2021-06-26

Abstract

Background: Interleukin (IL)-18 is produced mainly in the heart, and can be associated to the development of cardiac hypertrophy that leads to cardiac dysfunction. However, the effects of hypoxia on IL-18 expression and atrial natriuretic factor (ANF) secretion remain largely unknown.

Aim: To assess the effect of hypoxia on IL-18 production and its role in ANF secretion by using an isolated perfused beating rat atrial model.

Methods: The level of ANF in the perfusates was determined by radioimmunoassay, and the protein levels of Src, IL-18 and its receptors (IL-18-Rα and IL-18-Rβ), Rho guanine nucleotide exchange factor (RhoGEF) and RhoA, activating transcription factor 3 (ATF3), T cell factor (TCF) 3 and 4, and lymphoid enhancer factor (LEF) 1 in atrial tissue samples were detected by Western blotting.

Results: Hypoxia significantly upregulated the expression of non-receptor tyrosine kinase Src, and this effect was blocked by endothelin-1 receptor type A (BQ123) and type B (BQ788) antagonists. Hypoxia also enhanced the expression of RhoGEF and RhoA concomitantly with the upregulation of IL-18, IL-18-Rα and IL-18-Rβ. The hypoxia-induced RhoGEF and RhoA were abolished by Src inhibitor 1 (SrcI), and the protein levels of IL-18 and its two receptors were also blocked by SrcI. Moreover, the hypoxia-induced expression levels of ATF3, TCF3, TCF4 and LEF1 were repealed by IL-18 binding protein, and the hypoxia-promoted secretion of ANF was also obviously attenuated by this binding protein.

Conclusions: These findings imply that Src-IL-18 signaling is involved in the release of ANF in hypoxic beating rat atria.

Abstract

Background: Interleukin (IL)-18 is produced mainly in the heart, and can be associated to the development of cardiac hypertrophy that leads to cardiac dysfunction. However, the effects of hypoxia on IL-18 expression and atrial natriuretic factor (ANF) secretion remain largely unknown.

Aim: To assess the effect of hypoxia on IL-18 production and its role in ANF secretion by using an isolated perfused beating rat atrial model.

Methods: The level of ANF in the perfusates was determined by radioimmunoassay, and the protein levels of Src, IL-18 and its receptors (IL-18-Rα and IL-18-Rβ), Rho guanine nucleotide exchange factor (RhoGEF) and RhoA, activating transcription factor 3 (ATF3), T cell factor (TCF) 3 and 4, and lymphoid enhancer factor (LEF) 1 in atrial tissue samples were detected by Western blotting.

Results: Hypoxia significantly upregulated the expression of non-receptor tyrosine kinase Src, and this effect was blocked by endothelin-1 receptor type A (BQ123) and type B (BQ788) antagonists. Hypoxia also enhanced the expression of RhoGEF and RhoA concomitantly with the upregulation of IL-18, IL-18-Rα and IL-18-Rβ. The hypoxia-induced RhoGEF and RhoA were abolished by Src inhibitor 1 (SrcI), and the protein levels of IL-18 and its two receptors were also blocked by SrcI. Moreover, the hypoxia-induced expression levels of ATF3, TCF3, TCF4 and LEF1 were repealed by IL-18 binding protein, and the hypoxia-promoted secretion of ANF was also obviously attenuated by this binding protein.

Conclusions: These findings imply that Src-IL-18 signaling is involved in the release of ANF in hypoxic beating rat atria.

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Keywords

atrial natriuretic factor, endothelin-1, hypoxia, interleukin-18, non-receptor tyrosine kinase Src

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Title

Src-IL-18 signaling regulates the secretion of atrial natriuretic factor in hypoxic beating rat atria

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Online first

Article type

Original article

Published online

2021-06-26

DOI

10.33963/KP.a2021.0051

Pubmed

34176112

Keywords

atrial natriuretic factor
endothelin-1
hypoxia
interleukin-18
non-receptor tyrosine kinase Src

Authors

Xiang Li
Cheng-xi Wei
Cheng-zhe Wu
Lan Hong
Zhuo-na Han
Ying Liu
Wang Yue-ying
Xun Cui

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