Reactive Oxygen Species in Cellular Injury

Reactive Oxygen Species (ROS) in Cellular Injury

• Several molecules are generated during cellular injury, damaging membranes, proteins, and nucleic acids.
• Cells have inherent antioxidant compounds to limit damage.
• Cellular injury from ROS occurs when these defense mechanisms are overwhelmed.

Free Radicals

• Free radicals are chemical compounds with a single unpaired electron.
• Highly reactive and interact with adjacent molecules, releasing energy and altering them.
• Interact with lipids in cell membranes (peroxidation), proteins, and DNA, leading to damage.
• Lipid peroxidation is a chain reaction damaging cell membranes and causing further oxidation of membrane components.
• This imbalance between free radical generation and scavenging is called oxidative stress.

Mechanism of ROS

• Mitochondria are the primary source of endogenous reactive oxygen species (ROS).
• Excessive ROS production damages macromolecules (nucleic acids, proteins, and lipids).
• This leads to tissue damage in chronic/degenerative diseases.
• ROS further damages structures through lipid peroxidation.
• Activation of proteases disrupts the cytoskeleton, damaging cell structure.
• Disruption of lysosomal membranes releases damaging enzymes (e.g., DNAses, proteases), leading to cell death.

Reactive Oxygen Species Involvement in Cell Damage

• Mitochondria are the primary cellular source of reactive oxygen species.
• ROS can damage cell membranes, proteins, and DNA
• Imbalance between ROS production and scavenging is called oxidative stress and causes damage.
• ROS damage can involve inflammation, reperfusion injuries, altered metabolism, and exposure to exogenous chemicals or ionizing radiation.
• Damage may include lipid peroxidation, protein oxidation/cross-linking, and DNA strand breaks.

Sources of ROS Damage

• Mitochondria are the primary source of ROS in the cell.
• Other sources include: inflammation, reperfusion injury, altered metabolism, chemical exposure, and ionizing radiation.

Cellular Defense Mechanisms

• Cells have antioxidant compounds to mitigate ROS damage.
• Important enzymes involved in neutralizing ROS include superoxide dismutase (SOD), catalase, and glutathione peroxidase.
• Vitamins C, E, and carotenoids act as antioxidants.

Protective Mechanisms

• Cells have protective mechanisms against ROS-mediated injury.
• These include enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase.
• They neutralize damaging ROS, thereby preventing severe injury.
• Other protective factors include vitamins E and C and antioxidants in the diet.

Important Enzymes in Respiratory Burst

• NADPH oxidase is present in phagosomes (membrane-bound compartments).
• Along with NADPH, it uses oxygen to generate superoxide anions and hydrogen peroxide (H₂O₂).
• These oxygen metabolites are crucial for killing bacteria during the respiratory burst.
• Other key factors in the respiratory burst are oxygen, NADPH, NADP, and HMP shunt.

Cellular Structures Involved in ROS Neutralization

• Peroxisomes contain catalase, which neutralizes hydrogen peroxide.
• Mitochondria, cytosol, and peroxisomes contain important enzymes for ROS neutralization.

Additional Notes:

• The Haber-Weiss reaction is a cellular reaction producing hydroxyl radicals from hydrogen peroxide and superoxide, catalyzed by iron ions
• Reactive oxygen species are crucial in immune responses to bacteria.

This quiz explores the role of reactive oxygen species (ROS) in cellular injury. It covers their formation, mechanisms, and the impact of oxidative stress on cellular components such as lipids, proteins, and nucleic acids. Understand the delicate balance between free radicals and antioxidant defenses.