Implication of Thioredoxin 1 and Glutaredoxin 1 in H2O2-induced Phosphorylation of JNK and p38 MAP Kinases.

Background: Aerobic organisms continuously generate small amounts of Reactive Oxygen Species (ROS), which are involved in the oxidation of sensitive cysteine residues in proteins, leading to the formation of disulfide bonds. Thioredoxin (Trx1) and Glutaredoxin (Grx1) represent key antioxidant enzymes reducing disulfide bonds.

Objective: In this work, we have focused on the possible protective effect of Trx1 and Grx1 against oxidative stress-induced DNA damage and apoptosis-signaling, by studying the phosphorylation of MAP kinases.

Combined administration of membrane-permeable and impermeable iron-chelating drugs attenuates ischemia/reperfusion-induced hepatic injury.

Background: The underlying pathophysiological mechanisms of hepatic ischemia-reperfusion (I/R) injury have not been completely elucidated. However, it is well known that oxidative stress, caused by a burst of reactive oxygen species (ROS) production during the reperfusion phase, plays a crucial role. A growing body of evidence indicates that the intracellular availability of free iron represents a requirement for ROS-induced adverse effects, as iron catalyzes the generation of highly reactive free radicals.

Implication of Dietary Iron-Chelating Bioactive Compounds in Molecular Mechanisms of Oxidative Stress-Induced Cell Ageing.

One of the prevailing perceptions regarding the ageing of cells and organisms is the intracellular gradual accumulation of oxidatively damaged macromolecules, leading to the decline of cell and organ function (free radical theory of ageing). This chemically undefined material known as "lipofuscin," "ceroid," or "age pigment" is mainly formed through unregulated and nonspecific oxidative modifications of cellular macromolecules that are induced by highly reactive free radicals. A necessary precondition for reactive free radical generation and lipofuscin formation is the intracellular availability of ferrous iron (Fe) ("labile iron"), catalyzing the conversion of weak oxidants such as peroxides, to extremely reactive ones like hydroxyl (HO) or alcoxyl (RO) radicals.

Bioinspired tailoring of fluorogenic thiol responsive antioxidant precursors to protect cells against HO-induced DNA damage.

Natural antioxidants, like phenolic acids, possess a unique chemical space that can protect cellular components from oxidative stress. However, their polar carboxylic acid chemotype reduces full intracellular antioxidant potential due to limited diffusion through biological membranes. Here, we have designed and developed a new generation of hydrophobic turn-on fluorescent antioxidant precursors that upon penetration of the cell membrane, reveal a more polar and more potent antioxidant core and simultaneously become fluorescent allowing their intracellular tracking.

Iron homeostasis and oxidative stress: An intimate relationship.

Iron is a transition metal and essential constituent of almost all living cells and organisms. As component of various metalloproteins it is involved in critical biochemical processes such as transport of oxygen in tissues, electron transfer reactions during respiration in mitochondria, synthesis and repair of DNA, metabolism of xenobiotics, etc. However, when present in excess within cells and tissues, iron disrupts redox homeostasis and catalyzes the propagation of reactive oxygen species (ROS), leading to oxidative stress.