NADPH oxidase (NOX) in the heart : the interplay of NOX-derived ROS in β1-integrin-induced survival signalling

Moderate levels of reactive oxygen species (ROS) act as mediators in cellular signalling processes. An important source of cardiac ROS is the highly expressed NADPH oxidase (NOX) family isoform NOX2. However, little is known about whether NOX-derived ROS are protective in the heart.
In this study we show that CD29 (β1-integrin), a cell adhesion receptor highly expressed on cardiac muscle cells, induces NOX-dependent ROS. CD29 is known to be mandatory in cell growth and survival, and non-functional CD29 causes severe heart disease. We demonstrate that NOX2-derived ROS are essential for CD29-induced survival signalling, including the PI3K/PKB and MEK/ERK pathways. Furthermore, CD29-induced NOX-derived ROS are indispensible in the inhibition of the pro-apoptotic kinase GSK-3β, which we uncovered as a downstream target of both the ERK and PKB survival pathways in cardiac muscle cells. These findings clearly add to the growing body of evidence suggesting that moderate ROS levels are beneficial to the cell and highlight the crucial role of NOX2-derived ROS for cell survival in the heart.