Oxidative Damage in Rat Brain During Aging: Interplay Between Energy and Metabolic Key Target Proteins

Abstract

Aging is characterized by a gradual and continuous loss of physiological functions and responses particularly marked in the central nervous system. Reactive oxygen species (ROS) can react with all major biological macromolecules such as carbohydrates, nucleic acids, lipids, and proteins. Since proteins are the major components of biological systems and regulate multiple cellular pathways, oxidative damage of key proteins are considered to be the principal molecular mechanisms leading to age-related deficits. Recent evidences support the notion that a decrease of energy metabolism in the brain contribute to neuronal loss and cognitive decline associated with aging. In the present study we identified selective protein targets which are oxidized in aged rats compared with adult rats. Most of the oxidatively modified proteins we found in the present study are key proteins involved in energy metabolism and ATP production. Oxidative modification of these proteins was associated with decreased enzyme activities. In addition, we also found decreased levels of thiol reducing system. Our study demonstrated that oxidative damage to specific proteins impairs energy metabolism and ATP production thus contributing to shift neuronal cells towards a more oxidized environment which ultimately might compromise multiple neuronal functions. These results further confirm that increased protein oxidation coupled with decreased reducing systems are characteristic hallmarks of aging and aging-related degenerative processes.

Effects of Treating Old Rats with an AqueousAgaricus blazeiExtract on Oxidative and Functional Parameters of the Brain Tissue and Brain Mitochondria

“…However, it is likely that the antioxidant properties of the extract played an important role. This proposition bases on the fact that many alterations in enzymatic activities in the brain of old rats are accompanied by oxidative modifications in proteins such as carbonylations and nitrations [67]. In principle such modifications can be prevented by improving the antioxidant defenses of the cells, a task for which the A. blazei extract is well equipped as already discussed above.…”

Oxidative Damage Compromises Energy Metabolism in the Axonal Degeneration Mouse Model of X-Adrenoleukodystrophy

“…I mpaired bioenergetics and mitochondria metabolism, together with oxidative stress, are commonalities underlying age-related neurodegenerative diseases, such as Parkinson's (PD), Huntington's (HD) and Alzheimer's (AD) disease, Friedreich's ataxia, or amyotrophic lateral sclerosis (ALS), to cite a few (11,12,14,29,36,37,40). It has been postulated that oxidative stress in mitochondria can reduce the activities of their various proteins due to oxidative modifications (8,32,43,60,65).…”

Energy metabolism, proteotoxic stress and age-related dysfunction – Protection by carnosine

“…It is also observed that proteins bearing the effects of ROS attack accumulate with age (Di Domenico et al, 2010). Thus, it is frequently assumed that attack by ROS is a cause of ageing and age-related proteotoxicity.…”