Redox signaling during hypoxia in mammalian cells

Abstract

Hypoxia triggers a wide range of protective responses in mammalian cells, which are mediated through transcriptional and post-translational mechanisms. Redox signaling in cells by reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) occurs through the reversible oxidation of cysteine thiol groups, resulting in structural modifications that can change protein function profoundly. Mitochondria are an important source of ROS generation, and studies reveal that superoxide generation by the electron transport chain increases during hypoxia. Other sources of ROS, such as the NAD(P)H oxidases, may also generate oxidant signals in hypoxia. This review considers the growing body of work indicating that increased ROS signals during hypoxia are responsible for regulating the activation of protective mechanisms in diverse cell types.

Bis(thiosemicarbazone)copper(I) Complexes as Prospective Therapeutic Agents: Interaction with DNA/BSA Molecules, and In Vitro and In Vivo Anti‐Proliferative Activities

“…Recently, the cyclic voltammetric technique was successfully employed to understand the participation of copper(I) complexes in ROS production . The redox signaling can be related to cellular homeostasis in both normal and tumor cells . Generally, copper complexes can effectively kill cancer cells during the ROS generation i. e., O 2 •− , H 2 O 2 and HO • via incidence of redox processes.…”

“…[33] The redox signaling can be related to cellular homeostasis in both normal and tumor cells. [34] Generally, copper complexes can effectively kill cancer cells during the ROS generation i. e., O 2 * À [35] Generally, cells contain some biological radicals (RO * , ROO * , RS * etc), which showed high redox potentials, for instance, RO * (1.6 V), ROO * (~1.0 V) and RS * (e. g., cysteine; 0.9 V), and may efficiently participate in redox reaction. In order to evaluate the redox properties of newly synthesized copper(I) complexes (1À6), which show one electron transfer and the oxidation of Cu(I) to Cu(II) was observed in the range between 0.9 and 1.03 V. In addition, the complexes also show another oxidation peak at 1.62À1.73 V. The first peak resemble to irreversible oxidation processe localized at ligands since it is also seen in voltammogram of free ligands ( Figure S5), which confirms that the ligands does involved in the potential values of studied copper(I) complexes.…”

Oxygen, evolution and redox signalling in the human brain; quantum in the quotidian

“…While numerous models have been proposed (Neubauer & Sunderram, 2004), accumulating evidence suggests a central role for the mitochondrion, which makes intuitive sense given its intimate relationship with O 2 and the fact that cytochrome aa3 represents its terminal acceptor. More specifically, it has been suggested that hypoxia increases O 2 •− formation from Complex III of the electron transport chain possibly by increasing ubisemiquinone lifetime at the outer ubiquinone binding site (Q 0 ), with release to the intermembrane space and subsequent hydrogen peroxide formation triggering HIF-α stabilisation subsequent to PHD inactivation potentially related to phosphorylation or decreased bioavailability of Fe (II) (Chandel et al 1998;Bell et al 2007;Smith et al 2017; Fig. 4B).…”

The Role of Oxidative Stress in the Development of Systemic Sclerosis Related Vasculopathy

“…Hypoxia increases ROS production by a variety of mechanisms, triggering marked alterations in redox signaling (Smith et al, 2017). Furthermore, ROS upregulate vascular endothelial growth factor (VEGF) expression via activation of HIF-1, subsequently leading to angiogenesis (Arbiser et al, 2002; Xia et al, 2007).…”