Evidence for the Involvement of NADPH Oxidase in Adenosine Receptors-mediated Control of Coronary Flow Using A and A Knockout Mice

Overview

Journal Physiol Rep

Specialty Physiology

Date 2013 Oct 26

PMID 24159377

Citations 9

Authors

Mohammed S El-Awady

Uthra Rajamani

Bunyen Teng

Stephen L Tilley

S Jamal Mustafa

Affiliations

Soon will be listed here.

Abstract

The NADPH oxidase (Nox) subunits 1, 2 (gp91 ) and 4 are the major sources for reactive oxygen species (ROS) in cardiovascular system. In conditions such as ischemia-reperfusion injury and hypoxia, both ROS and adenosine are released suggesting a possible interaction. We hypothesized that ROS generated through Nox is involved in adenosine-induced coronary flow (CF) responses. Adenosine (10-10 M) increased CF in isolated hearts from wild type (WT; C57/BL6), A adenosine receptor (AR) knockout (AKO), AAR KO (AKO) and A and AAR double KO (A/ADKO) mice. The Nox inhibitors apocynin (10 M) and gp91 ds-tat (10 M) or the SOD and catalase-mimicking agent EUK134 (50 μM) decreased the adenosine-enhanced CF in the WT and all the KOs. Additionally, adenosine increased phosphorylation of p47-phox subunit and ERK 1/2 without changing protein expression of Nox isoforms in WT. Moreover, intracellular superoxide production was increased by adenosine and CGS-21680 (a selective A agonist), but not BAY 60-6583 (a selective A agonist), in mouse coronary artery smooth muscle cells (CASMCs) and endothelial cells (CAECs). This superoxide increase was inhibited by the gp91 ds-tat and ERK 1/2 inhibitor (PD98059). In conclusion, adenosine-induced increase in CF in isolated heart involves Nox2-generated superoxide, possibly through ERK 1/2 phosphorylation with subsequent p47-phox subunit phosphorylation. This adenosine/Nox/ROS interaction occurs in both CASMCs and CAECs, and involves neither A nor A ARs, but possibly A ARs in mouse.

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