Cell adhesion and integrin expression are modulated by oxidative stress in EA.hy 926 cells

Abstract

The effects of oxidative stress on integrin-mediated cell adhesion to the extracellular matrix (ECM) and related apoptosis were investigated using the EA.hy926 endothelial cells treated (or not) with two oxidants: the hypoxanthine/xanthine oxidase system (HX/XO) or the tert-butyl hydroperoxide (t-BHP) which both increased cell apoptosis. Cell adhesion onto vitronectin (Vn) and fibronectin (Fn) was increased at low concentrations of HX/XO (up to 5 mU/ml) or t-BHP (up to 125 microM) and prevented ROS-induced apoptosis. Flow cytometry analysis of integrin expression showed that the expression of integrin alphav and alpha5 subunits was, respectively, increased and decreased. Cell adhesion inhibition experiments using function-blocking monoclonal antibodies against integrin subunits indicated that alphavbeta1 and alphavbeta3 integrins were involved in adhesion of cells to Vn, and alphavbeta3 integrin played a major role in oxidant-treated cells. For adhesion to Fn, alpha5beta1 and alphavbeta1 integrins were required for oxidant-treated cells. Taken together, the results suggest that reactive oxygen species (ROS) produced either by HX/XO or t-BHP could affect expression and/or activation of specific integrins in the interaction of EA.hy926 cells with ECM.

Expansion on Extracellular Matrix Deposited by Human Bone Marrow Stromal Cells Facilitates Stem Cell Proliferation and Tissue-Specific Lineage Potential

“…Intracellular ROS plays an important role in cell adhesion, migration, and proliferation and thus is essential for cell survival. 16 A low concentration of ROS has a promotional effect on cell adhesion, 17 whereas a high level of ROS has an inhibitory influence on cell proliferation by arresting cell cycle at the G1, S, and G2 phases through downregulation of cyclin D1 and D3 signaling. 18 Our study demonstrated that ECM could attenuate ROS level in expanded cells, which benefited cell adhesion and survival.…”

Redox regulation of the actin cytoskeleton and its role in the vascular system

“…In liver sinusoidal endothelial cells exposed to prolonged high glucose, integrin αvβ3 and laminin expression are upregulated, and this response is significantly inhibited by N-acetyl-cysteine (NAC), suggesting that the expression of αvβ3 is dependent on ROS levels in these cells [130]. In addition, ROS increase αv and decrease α5 expression in endothelial cells, affecting adhesion to vitronectin or fibronectin [131]. In VSMCs, downregulation of the Nox4 activator Poldip2 increases β1 integrin expression, leading to increased collagen I expression [132].…”

Erythroid cells generated in the absence of specific 1-integrin heterodimers accumulate reactive oxygen species at homeostasis and are unable to mount effective antioxidant defenses

“…α5 to Fn or αv to vitronectin). [43][44][45][46][47] Furthermore, in fibroblasts, neural cells or macrophages, migratory signals elicited by α4β1 are distinct from those elicited in the same cells by α5β1. [33][34][35][36] Their motility was dependent on α5/FAK signaling, but this was dispensable for α4β1-mediated signaling mediated through c-Src activation instead.…”

“…Very little is known about the precise downstream signaling pathways that are integrin-dependent in erythroid cells, although more is known in non-hematopoietic cells. 33,35,[43][44][45][46][47][48] Thus, oxidative stress is assumed to modulate cell-to-cell adhesion by affecting expression of adhesion molecules (i.e. α5 to Fn or αv to vitronectin).…”