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Cells respond to heavy metal stress by activating signaling cascades regulating cellular proliferation and survival. We here demonstrate that the anti-apoptotic kinase Akt is activated in HepG2 human hepatoma cells exposed to copper or zinc ions. Cu2+- and Zn2+-induced phosphorylation of Akt was blocked by phosphoinositide 3-kinase (PI3K) inhibitors,(More)
According to the World Health Organization, from 2014, cardiovascular diseases (CVD) are the number one cause of death worldwide. One of the key players in maintaining proper cardiovascular function is the endothelium, the inner layer of all blood vessels. This monolayer of cells on one hand serves as a barrier between blood and the surrounding tissue and(More)
Reactive oxygen species (ROS) act as a double-edged sword in numerous cardiovascular conditions. In addition to their known detrimental effects on all cellular macromolecules, referred to as oxidative stress, lower amounts of ROS also directly modify molecules and thereby modulate their functions this process has been termed redox signalling. Both oxidative(More)
Nickel compounds may act as carcinogens, affecting both initiation and promotion stages of carcinogenesis due, in large parts, to their capability of inducing DNA damage and of modulating cellular signaling cascades known to affect cellular proliferation, respectively. We have previously demonstrated that the phosphoinositide 3-kinase (PI3K)/Akt signaling(More)
FHRE-Luc is a promoter reporter construct that is widely used to assess the activity of FoxO (forkhead box, class O) transcription factors. We here demonstrate that this promoter construct responds to exposure of HepG2 human hepatoma cells to known agonists of the aryl hydrocarbon receptor (AhR), 3-methylcholanthrene, benzo(a)pyrene, and(More)
SIGNIFICANCE Redox signaling is one of the key elements involved in cardiovascular diseases. Two important molecules are the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and the oxidoreductase thioredoxin-1 (Trx-1). Recent Advances: During the previous years, a lot of studies investigated Nrf2 and Trx-1 as protective proteins in(More)
The serine/threonine kinase Akt is a mediator of insulin effects on target cells and, as such, is a major regulator of fuel metabolism. Akt was demonstrated to be activated in a phosphoinositide 3'-kinase-dependent fashion by stressful stimuli, including reactive oxygen species (ROS) and certain heavy metal ions. This minireview focuses on activation of the(More)
The ubiquitously expressed aryl hydrocarbon receptor (AhR) induces drug metabolizing enzymes as well as regulators of cell growth, differentiation and apoptosis. Certain AhR ligands promote atherosclerosis, an age-associated vascular disease. Therefore, we investigated the role of AhR in vascular functionality and aging. We report a lower pulse wave(More)
The APEX nuclease (multifunctional DNA repair enzyme) 1 (APEX1) has a disordered N-terminus, a redox, and a DNA repair domain. APEX1 has anti-apoptotic properties, which have been linked to both domains depending on cell type and experimental conditions. AIMS As protection against apoptosis is a hallmark of vessel integrity, we wanted to elucidate whether(More)
Selenoenzymes and nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated phase II enzymes comprise key components of the cellular redox and antioxidant systems, which show multiple interrelations. Deficiency of the micronutrient selenium (Se) and impaired biosynthesis of selenoproteins have been reported to result in induction of Nrf2 target genes.(More)