Intervention strategies to inhibit protein carbonylation by lipoxidation‐derived reactive carbonyls

Abstract

Protein carbonylation induced by reactive carbonyl species (RCS) generated by peroxidation of polyunsaturated fatty acids plays a significant role in the etiology and/or progression of several human diseases, such as cardiovascular (e.g., atherosclerosis, long-term complications of diabetes) and neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and cerebral ischemia). Most of the biological effects of intermediate RCS, mainly alpha,beta-unsaturated aldehydes, di-aldehydes, and keto-aldehydes, are due to their capacity to react with the nucleophilic sites of proteins, forming advanced lipoxidation end-products (ALEs). Because of the emerging deleterious role of RCS/protein adducts in several human diseases, different potential therapeutic strategies have been developed in the last few years. This review sheds focus on fundamental studies on lipid-derived RCS generation, their biological effects, and their reactivity with proteins, with particular emphasis to 4-hydroxy-trans-2-nonenal (HNE)-, acrolein (ACR)-, malondialdehyde (MDA)-, and glyoxal (GO)-modified proteins. It also discusses the recently developed pharmacological approaches for the management of chronic diseases in which oxidative stress and RCS formation are massively involved. Inhibition of ALE formation, based on carbonyl-sequestering agents, seems to be the most promising pharmacological tool and is reviewed in detail.

Association between oxidative stress and nutritional status in the elderly

“…Experimental studies indicated that carnosine plays an important role as anti-aging molecule. 52 Carnosine also stimulates the enzyme calcium ATPase and the calcium pump. This is important because the transmission of nerve impulses depends on calcium.…”

Modern Pharmacological Approaches to Therapies: Substances Tested in Animal Models of Rheumatoid Arthritis

“…In recent years, methods based on chemiluminescence and fluorescence measurements have been widely used for determination of ROS, RNS and lipid peroxidation metabolites. Fluorescent protein adducts are derivatives formed by reaction of secondary metabolites of lipid peroxidation (especially HNE and MDA) with free amino groups of proteins (Aldini et al, 2007;Requena et al, 1996). In murine and human serum, albumin protein fraction was identified as the most fluorescent fraction of proteins (Tsuchida et al, 1985).…”

Interplay Between Oxidative and Carbonyl Stresses: Molecular Mechanisms, Biological Effects and Therapeutic Strategies of Protection

“…Different stages of RCS, ALE and AGE formation and AGE-mediated damage are suggested as therapeutic intervention strategies (Peyroux and Sternberg, 2006;Aldini et al, 2007;Peng et al, 2011). Peyroux and Sternberg (2006) classified these strategies as follows: (i) trapping of reactive dicarbonyl species, (ii) AGE cross-link cleavage, (iii) AGE receptor blocking, (iv) AGE receptor signalling blocking, (v) glycemia reduction by antidiabetic therapy, (vi) aldose reductase inhibition; (vii) shunting of trioses-phosphate toward the pentose-phosphate pathway by transketolase activation; (viii) antioxidant therapy by transition metal chelation and free radical scavenging.…”