Cholecystokinin regulates atrial natriuretic peptide secretion through activation of NOX4-Sirt1-LEF1 signaling in beating rat hypoxic atria.

Autor: Xu LJ; Department of Physiology, School of Medicine, Yanbian University, Yanji 133-002, China., Zhi MT; Department of Physiology, School of Medicine, Yanbian University, Yanji 133-002, China., Lin XX; Department of Physiology, School of Medicine, Yanbian University, Yanji 133-002, China., Li X; Department of Physiology, School of Medicine, Yanbian University, Yanji 133-002, China., Li ZY; Department of Physiology, School of Medicine, Yanbian University, Yanji 133-002, China; Institute of Clinical Medicine, Yanbian University, Yanji, 133-000, China. Electronic address: 15526771578@163.com., Cui X; Department of Physiology, School of Medicine, Yanbian University, Yanji 133-002, China; Cellular Function Research Center, Yanbian University, Yanji 133-002, China. Electronic address: cuixun@ybu.edu.cn.
Jazyk: angličtina
Zdroj: Peptides [Peptides] 2024 Nov; Vol. 181, pp. 171299. Date of Electronic Publication: 2024 Sep 24.
DOI: 10.1016/j.peptides.2024.171299
Abstrakt: The mammalian cardiac myocytes not only synthesize and secrete atrial natriuretic peptide (ANP), but also express cholecystokinin (CCK) and its receptors (CCK 1 R and CCK 2 R). However, atrial CCK expression patterns and its effects on ANP secretion during hypoxia are unclear. Therefore, this study is aimed to investigate the effect of hypoxia on the expression levels of CCK and its receptors, as well as the underlying mechanisms involved in regulating hypoxia-induced ANP secretion in isolated beating atria. The results of this study showed that acute hypoxia significantly upregulated expression of CCK and CCK 1 R as well as CCK 2 R through activation of hypoxia-inducible factor 1α-apelin signaling. Endogenous CCK induced by hypoxia markedly upregulated the expression of silent information regulator factor 2-related enzyme 1 (Sirt1) and its downstream nuclear factor erythroid‑2‑related factor 2 (Nrf2) via the activation of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), leading to increase of activating T cell factor (TCF) 3 and TCF4/ lymphoid enhancer factor (LEF) 1, ultimately promoting hypoxia-induced ANP secretion. In addition, siRNA-mediated knockdown of LEF1 dramatically attenuated hypoxia-induced increase of ANP expression in HL-1 atrial myocytes. These results indicated endogenous CCK induced by hypoxia promoted hypoxia-induced ANP secretion by activation of NOX4-Sirt1-TCF3/4-LEF1 signaling pathway.
Competing Interests: Declaration of Competing Interest All contributing authors declare no conflicts of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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