Oxidative stress
High oxidative a stress is known to cause global cellular damage by creating reactive oxygen species (ROS) which causes damage to proteins, lipids and DNA (15, 82). Oxidative stress increases protein phosphorylation, causing changes to signaling pathways. For example, several phosphatases involved in cancer, apoptosis and aging are inactivated under conditions of high oxidative stress (26). ROS is a known contributor to several diseases including Alzheimer’s, Parkinson’s, Huntington’s, kidney disease, and T2DM (25, 27, 105). Known mediators of oxidative stress include transition metals and mitochondrial dysfunction (15, 27). In this project, I will be studying how cellular iron regulation causes an increase in oxidative stress, contributing to cellular damage and disease. Aconitase is an important mediator of oxidative stress, metabolism and iron regulation.
Aconitase is an enzyme in the TCA cycle that is located in both the cytosol and mitochondria. It is a widely used marker of oxidative stress and is an important point of iron regulation (fig. 3). Aconitase is sensitive to oxidative stress because it contains iron sulfur clusters that are released under conditions of low iron or high oxidative stress. After aconitase releases its Fe-S clusters, it undergoes a conformational change and becomes iron regulatory protein 1 (IRP-1). This increases cellular iron absorption and decreases iron storage through regulating iron transport and storage proteins.
Aconitase catalyzes the conversion of citrate to isocitrate in the mitochondria and cytosol. In the mitochondria, aconitase is required for the TCA cycle to continue. In the case of high mitochondrial ROS production, aconitase becomes oxidized and no longer functions...
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...nd is the most likely candidate for increased ROS observed with doxorubicin administration. Through these mechanisms, doxorubicin works well in slowing the progression of cancer. However, side effects of this drug limit the total dosage a patient can receive.
Four therapies have been described to decrease the muscle toxicity of doxorubicin. First, use of the iron chelator dexrazoxane decreases muscle toxicity (36, 89).Second, aerobic exercise has been shown to protect against doxorubicin induced skeletal muscle apoptosis through decreasing autophagy signaling (50, 84, 85). Third, the mitochondrial antioxidant SS31 protects against doxorubicin induced apoptosis (32). Fourth, pretreatment of metformin, an anti-diabetic drug, decreases cardiomyocyte apoptosis (7, 8). The interaction of doxorubicin and metformin will be discussed in greater detail in upcoming sections.
Montaner, B. and Perez-Tomas, R. 2001. Prodigiosin-induced apoptosis in human colon cancer cells. Life sciences, 68 (17), p. 2025-2036.
Pharmaceuticals have examined and found to ”work by changing the biological functions of the target cells in the body through chemical agents“ (Doweiko, 2015, p. 16). ”Many people in the past have thought that drugs that
This leads to the continued release of ACTH, resulting in a surplus of 17-OHP, which is converted in the a...
It is used widely in medicine as a treatment for a number of serious illnesses, ranging from types of anaemia, to the treatment of certain types of cancer, and also in the battle against AIDS. Unfortunately certain athletes, who will do anything to win, have realised its ergogenic benefits, and also the severity of its misuse.
Chemotherapy is the treatment of a tumor with chemical agents to reduce mass or eradicate a tumor completely. There are certain mechanisms by which chemotherapy inhibits cancer. The first mechanism is cell death by cytotoxicity. Some chemical agents in certain amounts are toxic to cells. The cells die due to the toxic...
In a healthy and young body, both antioxidants and the cell’s own repair capabilities work together to keep the cell intact. However, if the cell has become way too damaged for quite some time and cannot manage all the lesions created by free radicals, it can lose its ability to deal with the damages. This can also be referred to as the oxidative stress that the cells incur. Thus, they die quickly or begin replicating their damaged forms, and create a domino effect of the body gradually not being able to continue maintaining proper functioning
Because the body, namely the “brain, heart, liver, kidneys, pancreas, and skeletal muscle, demand a finely tuned capacity for energy and lots of it, these tissues possess more mitochondria” (parkridge). When the mitochondria are not properly functioning for these organs, cell damage can occur.
Hemochromatosis is a disease which makes your body absorb all of the iron in food, instead of regulating iron intake. Hemochromatosis “attacks” the entire body, especially the places where most of the iron normally goes: the bloodstream and liver. Some symptoms of this disease are bone and joint discomfort, liver problems, irregular heartbeat, and an unusual bronzing of the skin. Armand Trousseau first described it in 1865 as Diabetes bronze, due to people with diabetes showing the bronze-skin symptom. It was thought to be quite rare at the time. About “⅓ or ¼ of people of Western European descent have th...
During the TCA cycle, pyruvate is oxidized to acetyl CoA, which undergoes a condensation reaction catalyzed by citrate synthase to form citrate. Citrate can then be isomerized to form isocitrate, which undergoes oxidative carboxylation that is catalyzed by isocitrate dehydrogenase, to form α -ketoglutarate. Succinyl CoA is then formed from the decarboxylation/oxidation of α -ketoglutarate, which is catalyzed by α -ketoglutarate dehydrogenase. Succinyl CoA can be used to form products including chlorophyll, heme, and prophyr...
Another study proposed that CR slowed aging process by increasing resistance to hyperoxidation. As aging progressed in yeast and other animals, the presence of free radicals increased in the cells. Usually, the levels of the...
...blood and increase the absorption and concentration of digoxin in the blood. This may reduce the effectiveness of ketoconazole or increase digoxin toxicity. Through unknown mechanisms, omeprazole may increase blood levels of saquinavir and reduce blood levels of nelfinavir and atazanavir, drugs that are used for treating patients with infection caused by the human immunodeficiency virus (HIV). Omeprazole can be contraindicated in patient with hepatic impairment thus doctors are advised not to prescribe more than 20mg daily of omeprazole for such patients. [1] [3] [4]
Oxidative stress results from an imbalance in oxidant production and antioxidant defense mechanisms; this means that either the overproduction of reactive oxygen and nitrogen species (ROS/RNS) and / or a decreased antioxidant capacity leads to
The mitochondria is an organelle which is generally an oval shape and is found inside the cytoplasm and is again apart of the eukaryotic cells. The main function of the mitochondria is to complete cellular respiration; in simple terms it acts like a digestive system to break down essential nutrients and to convert it into energy. This energy is usually found to in ATP which is a rich molecule taken from the energy stored in food. Furthermore, mitochondria stores calcium for signalling activities; such as heat, growth and death. They have two unique membranes and mitochondria isn’t found in human cells like the red blood cells yet liver and muscle cells are filled entirely with mitochondria.
... the development of chronic lesions. Both drugs may cause serious side effects and should be administered under medical supervision.
Many research try to find new ways of stopping the aging process. Research discovered that the damage to the molecules which make up out cells is done by highly unstable molecules called reactive oxygen species. Humans need oxygen to stay alive, as this plays an important role in the energy production of cells. Normally the oxygen molecules are converted into water, but sometimes when they don’t take up enough electrons they become highly reactive. These reactive oxygen species which are left after the energy production process can damage the biological molecules, mutate genes, damage lipids which make up the cell membra...