scholarly journals Protein damage, ageing and age-related diseases

Open Biology ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 180249 ◽  
Author(s):  
Anita Krisko ◽  
Miroslav Radman
Keyword(s):  
Oxidative Damage ◽  
Protein Damage ◽  
Death Studies ◽  
Root Cause ◽  
Age Related ◽  
Oxidative Protein Damage ◽  
Gompertz Law ◽  
Radiation Induced ◽  
Folded Proteins

Ageing is considered as a snowballing phenotype of the accumulation of damaged dysfunctional or toxic proteins and silent mutations (polymorphisms) that sensitize relevant proteins to oxidative damage as inborn predispositions to age-related diseases. Ageing is not a disease, but it causes (or shares common cause with) age-related diseases as suggested by similar slopes of age-related increase in the incidence of diseases and death. Studies of robust and more standard species revealed that dysfunctional oxidatively damaged proteins are the root cause of radiation-induced morbidity and mortality. Oxidized proteins accumulate with age and cause reversible ageing-like phenotypes with some irreversible consequences (e.g. mutations). Here, we observe in yeast that aggregation rate of damaged proteins follows the Gompertz law of mortality and review arguments for a causal relationship between oxidative protein damage, ageing and disease. Aerobes evolved proteomes remarkably resistant to oxidative damage, but imperfectly folded proteins become sensitive to oxidation. We show that α-synuclein mutations that predispose to early-onset Parkinson's disease bestow an increased intrinsic sensitivity of α-synuclein to in vitro oxidation. Considering how initially silent protein polymorphism becomes phenotypic while causing age-related diseases and how protein damage leads to genome alterations inspires a vision of predictive diagnostic, prognostic, prevention and treatment of degenerative diseases.

scholarly journals Age-dependent effect of oxidative stress on cardiac sarcoplasmic reticulum vesicles

2008 ◽  
pp. S49-S54
Author(s):  
E Babušíková ◽  
M Jeseňák ◽  
D Dobrota ◽  
N Tribulová ◽  
P Kaplán
Keyword(s):  
Oxidative Stress ◽  
Sarcoplasmic Reticulum ◽  
Oxidative Damage ◽  
Structural Changes ◽  
Membrane Surface ◽  
Thiobarbituric Acid ◽  
Surface Hydrophobicity ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Age Related

The oxidative stress hypothesis of aging suggests that accumulation of oxidative damage is a key factor of the alterations in physiological function during aging. We studied age-related sensitivity to oxidative modifications of proteins and lipids of cardiac sarcoplasmic reticulum (SR) isolated from 6-, 15- and 26-month-old rats. Oxidative stress was generated in vitro by exposing SR vesicles to 0.1 mmol/l FeSO4/EDTA + 1 mmol/l H2O2 at 37 degrees C for 60 min. In all groups, oxidative stress was associated with decreased membrane surface hydrophobicity, as detected by 1-anilino-8-naphthalenesulfonate as a probe. Structural changes in SR membranes were accompanied by degradation of tryptophan and significant accumulation of protein dityrosines, protein conjugates with lipid peroxidation products, conjugated dienes and thiobarbituric acid reactive substances. The sensitivity to oxidative damage was most pronounced in SR of 26-month-old rat. Our results indicate that aging and oxidative stress are associated with accumulation of oxidatively damaged proteins and lipids and these changes could contribute to cardiovascular injury.

scholarly journals Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Samuel Abokyi ◽  
Sze wan Shan ◽  
Chi-ho To ◽  
Henry Ho-lung Chan ◽  
Dennis Yan-yin Tse
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Mrna Levels ◽  
Neuroprotective Effects ◽  
Rpe Cells ◽  
Age Related ◽  
Protein Expressions

Trehalose is a natural dietary molecule that has shown antiaging and neuroprotective effects in several animal models of neurodegenerative diseases. The role of trehalose in the management of age-related macular degeneration (AMD) is yet to be investigated and whether trehalose could be a remedy for the treatment of diseases linked to oxidative stress and NRF2 dysregulation. Here, we showed that incubation of human retinal pigment epithelial (RPE) cells with trehalose enhanced the mRNA and protein expressions of TFEB, autophagy genes ATG5 and ATG7, as well as protein expressions of macroautophagy markers, LC3B and p62/SQTM1, and the chaperone-mediated autophagy (CMA) receptor LAMP2. Cathepsin D, a hydrolytic lysosomal enzyme, was also increased by trehalose, indicating higher proteolytic activity. Moreover, trehalose upregulated autophagy flux evident by an increase in the endogenous LC3B level, and accumulation of GFP-LC3B puncta and free GFP fragments in GFP-LC3 ̶ expressing cells in the presence of chloroquine. In addition, the mRNA levels of key molecular targets implicated in RPE damage and AMD, such as vascular endothelial growth factor- (VEGF-) A and heat shock protein 27 (HSP27), were downregulated, whereas NRF2 was upregulated by trehalose. Subsequently, we mimicked in vitro AMD conditions using hydroquinone (HQ) as the oxidative insult on RPE cells and evaluated the cytoprotective effect of trehalose compared to vehicle treatment. HQ depleted NRF2, increased oxidative stress, and reduced the viability of cells, while trehalose pretreatment protected against HQ-induced toxicity. The cytoprotection by trehalose was dependent on autophagy but not NRF2 activation, since autophagy inhibition by shRNA knockdown of ATG5 led to a loss of the protective effect. The results support the transcriptional upregulation of TFEB and autophagy by trehalose and its protection against HQ-induced oxidative damage in RPE cells. Further investigation is, therefore, warranted into the therapeutic value of trehalose in alleviating AMD and retinal diseases associated with impaired NRF2 antioxidant defense.

scholarly journals Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain.

1996 ◽  
Vol 93 (10) ◽  
pp. 4765-4769 ◽  
Author(s):  
M. J. Forster ◽  
A. Dubey ◽  
K. M. Dawson ◽  
W. A. Stutts ◽  
H. Lal ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Motor Skills ◽  
Protein Damage ◽  
Age Related ◽  
Oxidative Protein Damage ◽  
The Brain

scholarly journals Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

2020 ◽  
Vol 21 (20) ◽  
pp. 7660 ◽  
Author(s):  
Hafza Wajeeha Ejaz ◽  
Wei Wang ◽  
Minglin Lang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Damage ◽  
Senile Plaques ◽  
Copper Toxicity ◽  
Short Review ◽  
Current Status ◽  
Age Related ◽  
Cu Ions

Alzheimer’s disease (AD) is an irreversible, age-related progressive neurological disorder, and the most common type of dementia in aged people. Neuropathological lesions of AD are neurofibrillary tangles (NFTs), and senile plaques comprise the accumulated amyloid-beta (Aβ), loaded with metal ions including Cu, Fe, or Zn. Some reports have identified metal dyshomeostasis as a neurotoxic factor of AD, among which Cu ions seem to be a central cationic metal in the formation of plaque and soluble oligomers, and have an essential role in the AD pathology. Cu-Aβ complex catalyzes the generation of reactive oxygen species (ROS) and results in oxidative damage. Several studies have indicated that oxidative stress plays a crucial role in the pathogenesis of AD. The connection of copper levels in AD is still ambiguous, as some researches indicate a Cu deficiency, while others show its higher content in AD, and therefore there is a need to increase and decrease its levels in animal models, respectively, to study which one is the cause. For more than twenty years, many in vitro studies have been devoted to identifying metals’ roles in Aβ accumulation, oxidative damage, and neurotoxicity. Towards the end, a short review of the modern therapeutic approach in chelation therapy, with the main focus on Cu ions, is discussed. Despite the lack of strong proofs of clinical advantage so far, the conjecture that using a therapeutic metal chelator is an effective strategy for AD remains popular. However, some recent reports of genetic-regulating copper transporters in AD models have shed light on treating this refractory disease. This review aims to succinctly present a better understanding of Cu ions’ current status in several AD features, and some conflicting reports are present herein.

The conjugation of Cu/Zn superoxide dismutase (SOD) to O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (O-HTCC) enhances its therapeutic potential against radiation-induced oxidative damage

2016 ◽  
Vol 7 (9) ◽  
pp. 1826-1835 ◽  
Author(s):  
Linghua Xu ◽  
Xiaohu Ji ◽  
Nan Zhao ◽  
Chunxia Song ◽  
Fengshan Wang ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Oxidative Damage ◽  
Therapeutic Potential ◽  
Enzyme Conjugate ◽  
Radiation Induced

A novel polymer–enzyme conjugate, O-HTCC–SOD, was prepared to improve the therapeutic potential of SOD in vitro and in vivo.

Synthesis, Antioxidant and Anticancer Activities of Efficient Glutathione Peroxidase Mimic

2011 ◽  
Vol 282-283 ◽  
pp. 317-321
Author(s):  
Ting Ting Lin ◽  
Jun Qiu Liu
Keyword(s):  
Glutathione Peroxidase ◽  
Oxidative Damage ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Peroxidase Mimic ◽  
Age Related ◽  
Tnf Α ◽  
Dose Dependent

Glutathione peroxidase (GPX) is a well-known selenoenzyme that can protect cells against oxidative damage. A novel dicyclodextrinyl ditelluride (2-TeCD) compound was devised as a functional mimic of the GPX. The antioxidant effect of 2-TeCD was evaluated by its ability to protect mitochondria from oxidative damage. 2-TeCD could also suppress the TNF-α induced inflammatory effect on HUVECs surface in a dose-dependent manner. Meanwhile, 2-TeCD exhibited anti-proliferative property both in vitro and in vivo. These results indicate that 2-TeCD may be useful for developing medical agents in many pathological conditions such as cataract­, age-related diseases­, atherosclerosis, cancer and so on.

Age-related differences in oxidative protein-damage in young and senescent fibroblasts

2009 ◽  
Vol 483 (1) ◽  
pp. 127-135 ◽  
Author(s):  
Tobias Jung ◽  
Annika Höhn ◽  
Betul Catalgol ◽  
Tilman Grune
Keyword(s):  
Protein Damage ◽  
Age Related ◽  
Oxidative Protein Damage
Sign in / Sign up

Export Citation Format

Share Document