Protective effects of carnosine on dehydroascorbate-induced structural alteration and opacity of lens crystallins: important implications of carnosine pleiotropic functions to combat cataractogenesis

Abstract

The high level of dehydroascorbic acid (DHA) in the lenticular tissue is an important risk factor for the development of age-related cataracts. In this study, the effects of DHA on structure and function of lens crystallins were studied in the presence of carnosine using gel mobility shift assay, different spectroscopic techniques, and lens culture analysis. The DHA-induced unfolding and aggregation of lens proteins were largely prevented by this endogenous dipeptide. The ability of carnosine to preserve native protein structure upon exposure to DHA suggests the essential role of this dipeptide in prevention of the senile cataract development. Although the DHA-modified α-crystallin was characterized by altered chaperone activity, functionality of this protein was significantly restored in the presence of carnosine. The increased proteolytic instability of DHA-modified lens proteins was also attenuated in the presence of carnosine. Furthermore, the assessment of lens culture suggested that DHA can induce significant lens opacity which can be prevented by carnosine. These observations can be explained by the pleiotropic functions of this endogenous and pharmaceutical compound, notably by its anti-glycation and anti-aggregation properties. In summary, our study suggests that carnosine may have therapeutic potential in preventing senile cataracts linked with the increased lenticular DHA generation, particularly under pathological conditions associated with the oxidative stress.

Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1

“…The levels of these reactive species increased in a dose-dependent manner by Aβ1-42 oligomers, whereas they significantly diminished in the presence of carnosine (Figure 2 and Figure 3) in accordance to its antioxidant activity and the ability of this peptide to directly interact with these species, decreasing their availability [6,76]. In particular, part of the observed decreased toxicity could be due to an increased uptake of carnosine by immune cells under stress conditions [77], to the ability of this dipeptide to convert NO into its not-toxic end-product nitrite [6], and/or carnosine capability to disassemble aggregate structures already formed [78,79]. In accordance to the viability and NO and O 2 −• results, Figure 4A–C shows that the decrease in reactive species depends not only on the scavenging activity of carnosine [80] but also on the ability of this peptide to decrease the expression Aβ-induced enzymes related to oxidative and nitrosative stress.…”

“…(co-inc.) treatments, the latter gave always slightly stronger effects. The increased protective effect observed with carnosine in microglial cells after the co-incubation of Aβ monomers with a millimolar concentration of carnosine suggests that the anti-aggregation properties of carnosine [5,78,79] significantly contribute to increase the overall protective effects of carnosine against Aβ1-42 toxicity in addition to the antioxidant activity of this peptide. Furthermore, our data obtained with AFM suggest that carnosine might preserve Aβ monomers, which are essential for neuronal survival and maintaining neuronal glucose homeostasis [84,85], and it can also promote the dissociation of Aβ oligomers.…”

How Can Diet Affect the Accumulation of Advanced Glycation End-Products in the Human Body?

“…Carnosine has been described as having a hypoglycemic effect, an indirect intracellular antioxidant activity, anti-inflammatory properties and carbonyl-trapping capacities [ 71 ]. Naturally present in significant concentrations in the human lens, it was successfully tested as an antiglycation agent for the lens with the aim of delaying senile cataracts [ 72 , 73 ]. Retarding the tissue accumulation of AGEs with carnosine or certain derivatives of this dipeptide should be investigated further.…”

Carnosine improves diabetic retinopathy via the MAPK/ERK pathway

“…Carnosine has been revealed to be an effective scavenger for the removal of reactive carbonyl species, as determined in a mouse model of diabetic nephropathy, and the reactive species located in pancreatic β-cells (10,14). Javadi et al (15) demonstrated that carnosine primarily prevents dehydroascorbic acid-induced unfolding and the aggregation of lens proteins and significant lens opacity. Furthermore, other studies have revealed that carnosine exerts a positive effect on the prevention and treatment of DR, but it has no association with anti-oxidation and anti-glycosylation (16,17).…”