Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells

Abstract

Cell cycle progression is regulated by a wide variety of external factors, amongst them are growth factors and extracellular matrix factors. During the last decades evidence has been obtained that reactive oxygen species (ROS) may also play an important role in cell cycle progression. ROS may be generated by external and internal factors. In this overview we describe briefly the generation of ROS and their effects on processes that have been demonstrated to play an essential role in cell cycle progression, including such systems as signal transduction cascades, protein ubiquitination and degradation, and the cytoskeleton. These different effects of ROS influence cell cycle progression dependent upon the amount and duration of ROS exposure. Activation of growth factor stimulated signaling cascades by low levels of ROS result in increased cell cycle progression, or, in case of prolonged exposure, to a differentiation like growth arrest. From many studies it seems clear that the cyclin kinase inhibitor protein p21 plays a prominent role, leading to cell cycle arrest at higher but not directly lethal levels of ROS. Dependent upon the nature of p21 induction, the cell cycle arrest may be transient, coupled to repair processes, or permanent. At high concentrations of ROS all of the above processes are activated, in combination with enhanced damage to the building blocks of the cell, leading to apoptosis or even necrosis.

Silver Nanoparticles Induced RNA Polymerase-Silver Binding and RNA Transcription Inhibition in Erythroid Progenitor Cells

“…16,57,58 ROS might then cause secondary injuries, such as a blockade of signal transduction cascades, protein degradation, and cytoskeleton disruption. 59,60 In the current study, we did not observe significant ROS induction in MEL cells upon nAg treatment at various concentrations over time ( Figure S5A); however, there was still significant inhibition on globin transcription ( Figure S5B, P < 0.05), suggesting the inhibition of nAg on RNA polymerase activity is independent of ROS.…”

Point Mutations in the Proline-rich Region of p22 Are Dominant Inhibitors of Nox1- and Nox2-dependent Reactive Oxygen Generation

“…Evidence over the last decades shows that reactive oxygen species (ROS), 1 including superoxide anion, hydrogen peroxide, and their reaction products, play crucial roles in diverse physiological processes including growth (1), regulation of vasodilatation (2), hormone synthesis (3), sperm capacitation (4), fertilization (5), oxygen sensing (6), bone absorption (7), and the innate immune response (8 -10). However, until the last several years, the enzymes responsible for generating these ROS were unknown, except for the phagocyte NADPH oxidase, a superoxide-generating enzyme whose catalytic moiety, flavocytochrome b 558 , is composed of a large catalytic subunit (gp91 phox or Nox2) and a smaller subunit (p22 phox ).…”

Sorafenib-Induced Hepatocellular Carcinoma Cell Death Depends on Reactive Oxygen Species ProductionIn VitroandIn Vivo

“…ROS are chemically reactive molecules that fulfill essential functions in living organisms. A moderate increase in ROS can promote cell proliferation and differentiation (15,16), whereas excessive amounts of ROS can cause oxidative damages to lipids, proteins and DNA and lead to cell death (13,14). Several chemotherapeutic drugs exert their cytotoxic effects through the generation of ROS (17).…”