Significance. Oxidative stress provokes the peroxidation of polyunsaturated fatty acids in cellular membranes, leading to the formation of aldheydes that, due to their high chemical reactivity, are considered to act as second messengers of oxidative stress. Among the aldehydes formed during lipid peroxidation, 4-hydroxy-2-nonenal (HNE) is produced at a high level and easily reacts both with low-molecular-weight compounds and macromolecules, such as proteins and DNA. In particular, HNE-protein adducts have been extensively investigated in diseases characterized by the pathogenic contribution of oxidative stress, such as cancer, neurodegenerative, chronic inflammatory and autoimmune diseases. Recent advances. In this review we describe and discuss recent insights concerning the role played by covalent adducts of HNE with proteins in the development and evolution of those, among the above mentioned disease conditions, in which the functional consequences of their formation have been characterized. Critical Issue. Results obtained in recent years have shown that the generation of HNE-protein adducts can play important pathogenic roles in several diseases. However, in some cases, the generation of HNE-protein adducts can represent a contrast to the progression of disease or can promote adaptive cell responses, demonstrating that HNE is not only a toxic product of lipid peroxidation, but also a regulatory molecule, involved in several biochemical pathways. Future directions. In the coming years, the refinement of proteomical techniques, allowing the individuation of novel cellular targets of HNE, will lead to a better understanding the role of HNE in human diseases.
Role of 4-hydroxynonenal-protein adducts in human diseases
Arcaro, A.;Cetrangolo, G. P.;Lepore, A.;Gentile, F.Ultimo
2015-01-01
Abstract
Significance. Oxidative stress provokes the peroxidation of polyunsaturated fatty acids in cellular membranes, leading to the formation of aldheydes that, due to their high chemical reactivity, are considered to act as second messengers of oxidative stress. Among the aldehydes formed during lipid peroxidation, 4-hydroxy-2-nonenal (HNE) is produced at a high level and easily reacts both with low-molecular-weight compounds and macromolecules, such as proteins and DNA. In particular, HNE-protein adducts have been extensively investigated in diseases characterized by the pathogenic contribution of oxidative stress, such as cancer, neurodegenerative, chronic inflammatory and autoimmune diseases. Recent advances. In this review we describe and discuss recent insights concerning the role played by covalent adducts of HNE with proteins in the development and evolution of those, among the above mentioned disease conditions, in which the functional consequences of their formation have been characterized. Critical Issue. Results obtained in recent years have shown that the generation of HNE-protein adducts can play important pathogenic roles in several diseases. However, in some cases, the generation of HNE-protein adducts can represent a contrast to the progression of disease or can promote adaptive cell responses, demonstrating that HNE is not only a toxic product of lipid peroxidation, but also a regulatory molecule, involved in several biochemical pathways. Future directions. In the coming years, the refinement of proteomical techniques, allowing the individuation of novel cellular targets of HNE, will lead to a better understanding the role of HNE in human diseases.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
