Decoding Aging: Understanding the Complex Relationship among Aging, Free Radicals, and GSH.

María E López-Navarro,José Guadalupe Trujillo-Ferrara,Laura Itzel Quintas-Granados,Daniel Ramírez-Rosales,Mariana Jarquín-Martínez,Luis A Sánchez-Labastida,Marycarmen Godínez-Victoria,Luciano Saso

doi:10.1155/2020/3970860

María E López-Navarro, José Guadalupe Trujillo-Ferrara + Show 6 more

Open Access

https://doi.org/10.1155/2020/3970860

Copy DOI

Abstract

N-aryl maleimides can undergo a 1,4-Michael-type addition reaction with reduced glutathione (GSH), leading to a decreased concentration of GSH and an increased concentration of free radicals (FRs) in cells. GSH is a critical scavenging molecule responsible for protecting cells from oxidation and for maintaining redox homeostasis. N-aryl maleimides disturb redox homeostasis in cells because they scavenge thiol-containing molecules, especially GSH. This study aimed at measuring the concentrations of GSH and FRs by electronic paramagnetic resonance (EPR), in the brain and liver tissue of male Wistar rats (ex vivo) at different ages and after treatment with 3,5-dimaleimylbenzoic acid (3,5-DMB). Our results showed a relationship between age and the concentrations of GSH and FRs in cells. In young rats, the concentration of GSH was higher than in old rats, while the concentration of FRs was higher in adult rats than in young rats, suggesting an inverse relationship between GSH and FRs. On the other hand, the reaction of 3,5-DMB (an electrophilic maleimide) with cellular GSH increased the FR content. The results of this study contribute to the awareness that the process of aging implies not only a loss of tissue function but also essential changes in the molecular contents of cells, especially the concentrations of FRs and GSH.

Highlights

In the electron flow system, oxygen is the final single electron acceptor involved in the production of energy in the form of ATP
Theoretical descriptors obtained from computational calculations of 3,5-DMB, N-acetyl cysteine (NAC), cysteine, and GSH (Table 1) revealed that 3,5-DMB has the highest chemical potential (μ) and lowest global hardness (η)
We concluded that the thiol compound selectively reacts with the olefinic carbons of 3,5-DMB due to their local softness, and the reaction of thiol species with 3,5-DMB shows selectivity for vinylic carbon from the α,β-unsaturated group but not for the carbonyl carbon group

Summary

Introduction

In the electron flow system, oxygen is the final single electron acceptor involved in the production of energy in the form of ATP. Cell respiration is balanced by the rates of free radical (FR) generation and elimination, which result from cell metabolism by single electron transfer. Some molecules lose or accept a single electron, leaving one or more unpaired electrons. These molecules are highly reactive and unstable. The most abundant FRs in cells are reactive oxygen species (ROS) and reactive nitrogen species (RNS). Reactive oxygen and nitrogen species (RONS) refer to reactive radical and nonradical derivatives of oxygen and nitrogen, respectively. Air and water contamination, certain drugs, industrial solvents, radiation, and a diet rich in carbohydrates can give rise to RONS in biological systems [1]

Objectives

Results

Discussion

Conclusion