Human Serum Albumin Misfolding in Aging and Disease

• Published in: International journal of molecular sciences Vol. 23; no. 19; p. 11675
• Main Authors: Tsao, Francis H. C., Meyer, Keith C.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2022; MDPI
• Subjects: age; Aging; Albumin; Alzheimer's disease; Binding sites; Communication; Fluidity; Fluorescence; Human serum albumin; Hydrophobicity; Inflammation; Laboratory animals; Liposomes; Membranes; misfolding; Patients; Phospholipase A2; Phospholipids; Protein folding; Protein structure; Proteins; Sepsis; serum; Serum albumin; sPLA2; Stability; Temperature effects
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms231911675

Age-dependent conformational stability of human serum albumin was determined by the method of fluorescent bilayer liposome assay. After pre-heating at 80 °C, albumin in the sera of 74-year-old healthy subjects exhibited hydrophobic effects on liposomes and made liposomal membrane phospholipids more susceptible to hydrolysis by the lipolytic enzyme phospholipase A2. In contrast, albumin in the sera of 24-year-old individuals was stable at 80 °C and displayed no increased hydrophobic effects on liposomes. The results suggest that albumin in the sera of 74-year-old subjects is more easily converted to a misfolded form in which its protein structure is altered when compared to albumin in the sera of 24-year-old individuals. Misfolded albumin can lose its ability to carry out its normal homeostatic functions and may promote alterations in membrane integrity under inflammatory conditions. However, our investigation has limitations that include the lack of testing sera from large numbers of individuals across a broad range of age to validate our preliminary observations of age-dependent differences in albumin stability and its interactions with liposomes.