Reactive oxygen species in vascular endothelial cell motility. Roles of NAD(P)H oxidase and Rac1

Abstract

Reactive oxygen species (ROS) are acknowledged generally to be multi-faceted regulators of cellular functions that trigger various pathological states when present chronically or transiently at non-physiologically high levels. Here we focus on the physiological involvement of ROS in cellular motility, with special emphasis on endothelial cells (EC). An important source of ROS within EC is the non-phagocytic NAD(P)H oxidase, and the small GTPase Rac1 plays a central role in activating this complex. Rac1 is one of the three Rho-family molecules (Rac, Rho and Cdc42) involved in the control of the actin cytoskeleton in response to various signals. In this review we examine the evidence linking ROS production, Rac1 activation and actin organization to EC motility, considering mechanisms for direct interaction of ROS and actin and the effects of ROS on proteins that regulate the actin cytoskeleton. The accumulated evidence suggests that ROS are important regulators of the actin cytoskeletal dynamics and cellular motility, and more in-depth studies are needed to understand the underlying mechanisms.

NAD(P)H Oxidase Mediates TGF-β1–Induced Activation of Kidney Myofibroblasts

“…NAD(P)H oxidases have been linked to a variety of cellular functions, including proliferation, migration, hypertrophy, regulation of metalloproteinases, matrix synthesis, cell senescence, and contraction. 28,29,36,[52][53][54] Indeed, differential roles of Nox1 and Nox4 in vascular smooth muscle cells have been correlated with differential compartmentalization in specific signaling domains in the membrane and focal adhesions. 55 Such observations combined with the differential expression of multiple Nox proteins in vascular smooth muscle in vitro and during restenosis 56 suggest distinct functions for these proteins.…”

Redox regulation of anoikis resistance of metastatic prostate cancer cells: key role for Src and EGFR-mediated pro-survival signals

“…The state of the art strongly implicates ROS, and in particular hydrogen peroxide and the superoxide anion radical, in cell adhesion (Chiarugi et al, 2003; Chiarugi and Fiaschi, 2007;Taddei et al, 2007), motility (Moldovan et al, 2006;Wu et al, 2008), cell transformation by oncogenes as Ras or Bcr-Abl (Wu, 2006), regulation of proteolytic degradation of ECM by matrix metalloproteinases (Nelson and Melendez, 2004), as well as in the acquisition of an invasive phenotype through epithelial-to-mesenchimal transition (Radisky et al, 2005;Cannito et al, 2008). Our present data enlarge the horizon for redox cancer biology and propose these oxidant molecules as central players in another key point for metastatic cells allowing them to spread metastases to distant organs, that is, the resistance to anoikis.…”

Tumor metabolism, cancer cell transporters, and microenvironmental resistance

“…In the early 1920s, a technician at Otto Warburg's lab spilled NaHCO 3 by accident and created an opportunity for Otto Warburg to observe that those cancer cells became highly fermentative. This has led to the development of the Warburg hypothesis that states that the driver for tumor development is a mitochondrial insult that leads to insufficient cellular respiration, explaining why even in the presence of adequate oxygen tumor cells preferentially turn to fermentation of lactic acid for an energy supply ''Warburg Effect'' 1 .…”

“…Furthermore, PPP maintains cellular redox status by providing a reduced form of glutathione which removes reactive oxygen species (ROS). Although the generation of ROS is an indication of cell death or induction of gene variation (mutation), ROS are also signaling molecules that are useful in the manipulation of cellular migration [3][4][5][6] . The generation of lactic acid is very helpful in allowing the progression of metastasis.…”