Oxidative Modifications in Tissue Pathology and Autoimmune Disease

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• Autoimmune syndromes involve cellular and tissue abnormalities influenced by microenvironmental factors like reactive oxygen species (ROS).
• Genetic, epigenetic, and environmental factors converge to cause B and T lymphocyte autoimmunity and tissue damage.

Purpose of the Study:

• To review how oxidative stress impacts post-translational protein modifications and gene expression in autoimmunity.
• To explore the role of ROS in altering self-proteins and their potential as biomarkers.
• To discuss pathways affected by ROS for potential therapeutic interventions in autoimmune diseases.

Main Methods:

• Review of literature on oxidative stress, protein modifications, and autoimmune disease pathways.
• Analysis of how ROS directly and indirectly affect protein structure and function.
• Examination of ROS effects on gene expression, DNA methylation, and cellular processes like apoptosis and NETosis.

Main Results:

• Oxidative stress amplifies carbonyl modifications and induces nonenzymatic (deamidation, isoaspartate) and enzymatic (citrullination) modifications of self-proteins.
• ROS directly impact DNA methylation, influencing gene expression, chromosome inactivation, and genetic element silencing.
• ROS trigger apoptosis and NETosis, releasing modified intracellular autoantigens, which can drive autoimmune responses.

Conclusions:

• Oxidative stress significantly contributes to autoimmunity through diverse post-translational protein modifications and altered gene expression.
• ROS-induced modifications of self-proteins are critical in autoimmune pathogenesis and may serve as valuable biomarkers.
• Targeting ROS-affected pathways offers promising therapeutic strategies for managing autoimmune disease onset and progression.