Category: REDOX Signaling

Redox regulation of development and regeneration

https://doi.org/10.1016/j.gde.2019.06.002Get rights and content

Oxygen is essential to contemporary life, providing the major electron sink underlying cellular energy metabolism. In addition to providing energy, largely involving redox reactions within mitochondriaoxidative metabolism produces reactive byproducts that are damaging to cellular components. Eukaryotic organisms have evolved multiple physiological mechanisms and signaling pathwaysto deal with fluctuating levels of oxygen and reactive oxygen species (ROS), and many of these are used in animals to regulate developmental processes. Here we review recent findings showing how mitochondria, ROS and hypoxia signaling contribute to the regulation of early axial patterning in embryos, to nervous system development, and to the regulation of cell proliferation and differentiation during development and regeneration.

Categories: REDOX Signaling

Do Some Vitamins Do More Harm than Good?

Novel prize winner James Watson, discoverer of the DNA double helix, in Oxidants, antioxidants and the current incurability of metastatic cancers proposed commonly consumed free-radical-destroying antioxidative nutritional supplements may have caused more cancers than they have prevented. This view is supported by metastudies e.g. analyzing 68 randomized trials with 232,606 participants (385 publications) and reviews showing the unfulfilled promises of antioxidant agents.

His hypothesis was that much of late-stage cancer’s untreatability may arise from its possession of too many antioxidants, and the time has come to seriously ask whether antioxidant use much more likely causes than prevents cancer. In 2014 James Watson came up with a radical theory for diabetes, dementia, heart disease and cancer where he wrote:

The fundamental cause, I suggest, is a lack of biological oxidants, not an excess.

Lancet

This also explains why metformin—the most commonly used drug to treat type 2 diabetes and physical exercise seems to be beneficial for several of the same diseases, including cancer, Alzheimer’s disease, and cardiovascular disease.

Watson believes that rather than being wholly bad, oxidizing molecules, such as hydrogen peroxide, are crucial for the body’s health. In particular, he points out that hydrogen peroxide goes to work in a cellular organ called the endoplasmic reticulum, where it ensures proteins are stable. If the REDOX level is disturbed, and levels of oxidants are too low, he suggests, the proteins become misshapen and cause the inflammation that damages the pancreas. And a raft of other diseases.

All in all, this opens the door to manipulating levels of reactive oxidizing molecules (ROS) for treating a host of chronic diseases that have thus far eluded medical science. Different ROS levels produce different outcomes with deleterious or beneficial effects. While there is still considerable controversy as to whether ROS modulation by either antioxidant supplementation or inhibition is clinically beneficial or detrimental for cancer treatment, supplementation with REDOX signaling molecules using products such as ASEA with an aim to restore optimal levels of ROS may potentially be a promising adjunctive strategy in anticancer therapies.

Categories: REDOX Signaling

REDOX Signaling Molecules

Reduction oxidation (REDOX) reactions are central to life and when altered, they can promote disease progression.  It is now clear that some ROS, such as hydrogen peroxide (H2O2), can act as messengers both in the extracellular environment and within cells. Mitochondria, the main cell power source, seems to be an important redox signaling node, central to metabolism, oxidative phosphorylation, the citric acid cycle, fatty acid oxidation, the urea cycle and the biosynthesis of iron-sulfur centers. Furthermore, mitochondria have key roles in cell death, calcium homeostasis, and oxygen sensing, proliferation, and angiogenesis – the growth of new blood vessels. Consequently, mitochondria are at the core of many biological processes, and redox signals to and from this organelle help to integrate mitochondrial function with the health of the cell and the organism.

Redox imbalance is expressed in one of two ways: a predominance of oxidative stress-related symptoms and signs (similar to rusting but in a biological sense), or a predominance of inflammatory (reactive) signs and symptoms. Health can be achieved by addressing imbalances in these areas and then moving the REDOX needle back to the balance point.

Our genetic blueprints have created a tendency to lean one direction or the other. We can choose to provide health support by addressing our REDOX potential. This is done primarily through lifestyle adjustments and also by supplementing with REDOX signaling molecules. An effective response to health challenges moves the balance back to the middle. For example, the management of cancer would involve reducing inflammation, the reactive response, rather than oxidative stress.

Categories: REDOX Signaling