Oxidative Modifications of Albumin Cysteine-34: A Biomarker of Oxidative Stress and Therapeutic Target

Dear Colleagues,

Human Serum Albumin (HSA) contains a single unbound cysteine residue, Cys34, which serves as the primary source of thiols in the bloodstream, accounting for approximately 80% of the total thiol pool. This residue is highly reactive and capable of interacting with both radical and non-radical oxidants, as well as electrophilic compounds. The reduced form of albumin, known as mercaptoalbumin (HSA-SH), is a key regulator of the redox state in extracellular compartments, including plasma and interstitial fluids.

Even under physiological conditions, HSA-SH undergoes significant oxidation, forming both reversible (mainly cysteinylated, HSA-S-S-Cys) and irreversible derivatives (such as sulfinic and sulfonic forms). These oxidative modifications increase notably with aging and in conditions characterized by oxidative stress.

Alterations in the levels of Cys34 and its oxidative forms have been observed in various oxidative stress-related diseases, including cardiovascular disease and chronic kidney disease. While the role of Cys34 and its oxidized forms as biomarkers of oxidative stress is well established, its involvement in the onset and progression of these diseases remains less clear. Recent findings, however, suggest that oral treatment with N-acetyl-cysteine (NAC) can regenerate mercaptoalbumin, offering potential therapeutic insights.

Despite these advances, several key aspects require further investigation: the precise role of Cys34 as an extracellular antioxidant, the endogenous mechanisms that maintain the balance between reduced and oxidized forms, its contribution to the development and progression of oxidative stress-based diseases, and the pharmacological potential of treatments that restore mercaptoalbumin.

We invite researchers to contribute critical reviews and original research articles on recent advances in the study of Cys34 oxidative modifications.

Potential topics include, but are not limited to, the following:

• Analytical methods for measuring Cys34 modifications;
• Cys34 and its modifications as biomarkers of systemic oxidative stress;
• Pharmacological strategies to regenerate mercaptoalbumin from its oxidized states;
• The impact of environmental stressors on Cys34 modifications;
• The role of Cys34 modifications in disease pathophysiology;
• Endogenous mechanisms for maintaining mercaptoalbumin levels.

Prof. Dr. Giancarlo Aldini
Dr. Alessandra Altomare
Dr. Giovanna Baron
Guest Editors

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• Cys34
• cysteine residue
• mercaptoalbumin
• oxidative stress
• oxidative stress-based diseases