Current Probes for Imaging Carbonylation in Cellular Systems and Their Relevance to Progression of Diseases

Abstract

Oxidative stress resulted from reactive oxygen or nitrogen species in biological systems has a significant role in the diagnosis/progression of several human diseases. Human diseases associated with oxidative stress include Alzheimer's disease, chronic lung disease, chronic renal failure, cancer, diabetes, and fibrosis. In oxidative stress conditions, carbonylation process can be described as one of the most common modifications in biomolecules that takes place in the presence of carbonyl (C = O) groups which are introduced into molecules by direct metal-catalyzed oxidation of certain amino acids or indirectly by reaction with the oxidation of lipids and sugars. At a molecular cellular level, carbonylation can cause some defective biological consequences or chemical transformations in cells. During this process, specifically, carbonylated proteins can be accumulated in cells and trigger to develop some diseases in human body. The role of the accumulation of carbonylated proteins in the progression of several diseases has also been reported in the literature, such as neurodegenerative diseases, diabetes, obesity, aging, and cancer. Early detection of carbonylation process is, therefore, very critical to monitor these diseases at an early stage. Finding a suitable biomarker or probe is very challenging due to the need for multiple criteria: high fluorescence efficiency, stability, toxicity, and permeability. If they are designed with a good strategy, these probes are highly effective in cell biology applications and they can be used as good diagnostic tools for monitoring oxidative stress-induced carbonylation in relevant diseases. This review highlights the design and use of recent fluorescent probes for visualization of carbonylation in cellular systems and the relationship between oxidative stress and carbonyl species for causing long-term disease complications.

Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System

“…Protein oxidation can be estimated by carbonylation, which results from the direct oxidation of amino acid side chains and from oxidative cleavage of protein. Carbonyls are difficult to induce and therefore may indicate a more severe state of OS [55,56]. In this study, there was a tendency of carbonylation to be reduced in patients who were treated with Vit E. This suggests that the low levels of Vit C found in patients requires its supplementation in combination with Vit E to reduce carbonyls [57].…”

Iron scavenging and suppression of collagen cross-linking underlie antifibrotic effects of carnosine in the heart with obesity

“…Structural changes in proteins caused by carbonylation leads to protein unfolding and polymerization, ultimately leading to formation of insoluble cross-linked protein aggregates. These protein aggregates evade proteasomal degradation, which prolongs their turnover rate and enhances their accumulation ( Negre-Salvayre et al, 2008 ; Dilek, 2022 ).…”

Modeling Side Chains in the Three-Dimensional Structure of Proteins for Post-Translational Modifications

“…For example, PTMs play an important role in regulation of enzyme activity, protein transport, and changing of protein stability [5,6]. Non-enzymatic PTMs, such as carbonylation and oxidation, often occur as a consequence of oxidative stress and are considered a ubiquitous mechanism for non-specific protein damage associated with age-related disorders, including neurodegenerative diseases, cancer, and diabetes mellitus [7,8]. It is important to note that amino acids often undergo significant changes in their physicochemical properties upon modification, which sometimes dramatically alters the structure of the affected protein and its dynamics and ability to interact with the environment and other proteins [3,9].…”