Reactive oxygen species (ROS)- Introduction, Types, Sources, Scavenging Enzymes, Cancer

Introduction:

Reactive oxygen species (ROS) are highly reactive molecules that are generated as natural byproducts of cellular metabolism.

They include free radicals such as superoxide (O2−), hydroxyl radical (OH−), and non-radical molecules like hydrogen peroxide (H2O2) and singlet oxygen (O2).

ROS play important roles in cellular signaling and defense against pathogens, but can also cause damage to cellular components like proteins, lipids, and DNA if they accumulate in excess.

ROS are normally kept in check by a complex system of antioxidant enzymes and molecules, but an imbalance between ROS production and antioxidant defenses can lead to oxidative stress, which has been implicated in a wide range of diseases including cancer, cardiovascular disease, neurodegenerative disorders, and aging.

Fig: Types of Reactive oxygen species (ROS)

Sources:

ROS are produced in various cellular processes, including cellular respiration, metabolism, and immune response.

In addition to being produced by mitochondrial oxidative metabolism, reactive oxygen species (ROS) are also produced by cells in reaction to xenobiotics, cytokines, and bacterial invasion.

During cellular respiration, the electron transport chain in mitochondria generates ROS as a natural byproduct of the production of ATP, the energy currency of the cell.

ROS can also be generated during metabolism of certain molecules, such as glucose, fats, and amino acids, through a process called auto-oxidation.

Immune cells, such as macrophages and neutrophils, produce ROS as a defense mechanism against pathogens. These cells use ROS to destroy invading pathogens, but excessive ROS production can also lead to tissue damage.

Environmental factors such as exposure to radiation, toxins, and pollutants can also increase ROS production.

Fig: Sources of Reactive oxygen species (ROS)

Regulation of ROS:

Reactive Oxygen Species (ROS) are important signaling molecules in cells, but they can also cause cellular damage if not properly regulated. To maintain a healthy balance of ROS, cells have evolved several mechanisms to control ROS production and remove excess ROS. Here are some of the ways cells regulate ROS:

• Antioxidant enzymes: Cells produce a variety of antioxidant enzymes, including superoxide dismutase (SOD), catalase, and glutathione peroxidase, which can neutralize ROS and prevent cellular damage.
• Antioxidant enzymes: Cells produce a variety of antioxidant enzymes, including superoxide dismutase (SOD), catalase, and glutathione peroxidase, which can neutralize ROS and prevent cellular damage.
• Non-enzymatic antioxidants: Cells also contain non-enzymatic antioxidants such as vitamins C and E, and glutathione, which can scavenge ROS and protect against oxidative stress.
• Redox signaling: ROS can act as signaling molecules that activate or inhibit various signaling pathways, depending on the type and amount of ROS produced. Cells use complex signaling networks to monitor ROS levels and respond accordingly.
• Repair mechanisms: Cells have repair mechanisms that can repair cellular damage caused by ROS, such as DNA repair mechanisms.
• Elimination of ROS: Cells use various mechanisms to eliminate excess ROS, including excretion through the urine, degradation by enzymes, and recycling of oxidized molecules.
• Regulation of ROS-generating enzymes: Cells can regulate the activity of enzymes that generate ROS, such as NADPH oxidase, to control ROS production.
• Environmental factors: Exposure to certain environmental factors such as radiation, pollutants, and toxins can increase ROS production. Therefore, minimizing exposure to these factors can help to regulate ROS production.

Measuring reactive oxygen species:

Measuring reactive oxygen species (ROS) can be challenging because they are highly reactive and have a short half-life. However, there are several methods available to measure ROS levels in cells or tissues. Here are some commonly used methods:

• Fluorescent probes: Fluorescent probes such as dichlorofluorescin (DCF) and dihydroethidium (DHE) are commonly used to measure ROS levels. These probes are oxidized by ROS and emit fluorescence, which can be detected using a fluorometer or fluorescence microscope.
• Electron paramagnetic resonance (EPR): EPR is a method that can directly detect and quantify free radicals, including ROS. This method involves the use of a spin-trapping agent that reacts with free radicals to produce a stable radical species that can be detected by EPR.
• Amplex Red assay: The Amplex Red assay is a method that measures hydrogen peroxide (H2O2), which is a type of ROS. The assay involves the reaction of H2O2 with Amplex Red and horseradish peroxidase (HRP), which produces a fluorescent product that can be detected using a fluorometer.
• High-performance liquid chromatography (HPLC): HPLC can be used to measure levels of specific ROS, such as superoxide and hydrogen peroxide, by separating and quantifying the products of their reactions with specific probes.
• Oxidative stress biomarkers: Biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG) and protein carbonyls can be measured as indicators of oxidative stress, which is caused by excess ROS production.

ROS Scavenging Enzymes

ROS scavenging enzymes are enzymes that help to neutralize reactive oxygen species (ROS), which are molecules that can cause oxidative damage to cells and tissues. ROS scavenging enzymes are crucial for maintaining cellular health and preventing oxidative damage. Reactive oxygen species (ROS), which are generated as byproducts of normal cellular metabolism and in response to environmental stressors, can cause damage to cellular components such as lipids, proteins, and DNA. This damage can lead to cellular dysfunction and contribute to the development of a variety of diseases including cancer, cardiovascular disease, and neurodegenerative disorders.

ROS scavenging enzymes help to neutralize ROS and prevent their harmful effects. For example, superoxide dismutase (SOD) converts superoxide radicals into hydrogen peroxide and oxygen, which can then be further metabolized by other enzymes. Catalase converts hydrogen peroxide into water and oxygen, while glutathione peroxidase and peroxiredoxins reduce hydrogen peroxide and organic hydroperoxides to less harmful products. In addition to their role in preventing oxidative damage, ROS scavenging enzymes also play important roles in regulating cellular signaling pathways. For example, the redox state of thioredoxin, a key ROS scavenging enzyme, is involved in the regulation of protein function and signaling pathways involved in cell growth and survival.

Fig: Subcellular ROS production by light and detoxification by antioxidants in a plant cell

Role of ROS in aging and cancer:

Aging: ROS have been shown to damage cellular components such as DNA, proteins, and lipids, leading to cellular senescence and ultimately aging. ROS-induced oxidative stress is believed to be a major contributor to the aging process.

Cancer: ROS have been shown to play a role in the development of cancer. Excessive ROS can cause DNA damage and mutations, which can lead to the formation of cancerous cells. ROS also promote tumor growth by activating signaling pathways that support cell proliferation and survival.

Cell Signaling: ROS can act as signaling molecules, playing a role in cellular processes such as gene expression, inflammation, and cell growth. In cancer, ROS can activate oncogenic signaling pathways that promote cell growth and proliferation.

Immune Response: ROS play a role in the immune response by killing pathogens and infected cells. However, excessive ROS can damage healthy cells and tissues, leading to inflammation and autoimmune diseases.

Therapeutic Target: ROS have been targeted for cancer therapy, as cancer cells often have higher levels of ROS than normal cells. Targeting ROS can induce cancer cell death while sparing normal cells. However, targeting ROS can also cause side effects, such as oxidative damage to healthy tissues.

References:

• Caverzan, A., Casassola, A. and Brammer, S.P., 2016. Reactive oxygen species and antioxidant enzymes involved in plant tolerance to stress. Abiotic and biotic stress in plants-recent advances and future perspectives, 17, pp.463-480.
• Krumova, K. and Cosa, G., 2016. Overview of reactive oxygen species.
• Finkel, T., 2011. Signal transduction by reactive oxygen species. Journal of Cell Biology, 194(1), pp.7-15.
• Hancock, J. T.; Desikan, R.; Neill, S. J. Role of Reactive Oxygen Species in Cell Signaling Pathways. Biochemical and Biomedical Aspects of Oxidative Modification 2001, 29(2), 345–350.