Abstract:
:Alzheimer disease (AD) is an age-related neurodegenerative disease characterized by the presence of three pathological hallmarks: synapse loss, extracellular senile plaques (SP) and intracellular neurofibrillary tangles (NFTs). The major component of SP is amyloid β-peptide (Aβ), which has been shown to induce oxidative stress. The AD brain shows increased levels of lipid peroxidation products, including 4-hydroxy-2-nonenal (HNE). HNE can react covalently with Cys, His, or Lys residues on proteins, altering structure and function of the latter. In the present study we measured the levels of the HNE-modified lipoic acid in brain of subjects with AD and age-matched controls. Lipoic acid is a key co-factor for a number of proteins including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, key complexes for cellular energetics. We observed a significant decrease in the levels of HNE-lipoic acid in the AD brain compared to that of age-matched controls. To investigate this phenomenon further, the levels and activity of lipoamide dehydrogenase (LADH) were measured in AD and control brains. Additionally, LADH activities were measured after in-vitro HNE-treatment to mice brains. Both LADH levels and activities were found to be significantly reduced in AD brain compared to age-matched control. HNE-treatment also reduced the LADH activity in mice brain. These data are consistent with a two-hit hypothesis of AD: oxidative stress leads to lipid peroxidation that, in turn, causes oxidative dysfunction of key energy-related complexes in mitochondria, triggering neurodegeneration. This study is consonant with the notion that lipoic acid supplementation could be a potential treatment for the observed loss of cellular energetics in AD and potentiate the antioxidant defense system to prevent or delay the oxidative stress in and progression of this devastating dementing disorder.
journal_name
Redox Bioljournal_title
Redox biologyauthors
Hardas SS,Sultana R,Clark AM,Beckett TL,Szweda LI,Murphy MP,Butterfield DAdoi
10.1016/j.redox.2013.01.002subject
Has Abstractpub_date
2013-01-30 00:00:00pages
80-5issn
2213-2317pii
REDOX22journal_volume
1pub_type
杂志文章相关文献
Redox Biology文献大全abstract::Oxidative stress is reported to regulate several apoptotic and necrotic cell death pathways in auditory tissues. Poly(ADP-ribose) polymerase-1 (PARP-1) can be activated under oxidative stress, which is the hallmark of parthanatos. Autophagy, which serves either a pro-survival or pro-death function, can also be stimula...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2017.10.002
更新日期:2018-04-01 00:00:00
abstract::We have previously demonstrated that DGLA treatment along with Delta-5-Desaturase (D5D) siRNA in various types of cancer cells enhances the formation of 8-HOA from COX-2-catalyzed DGLA peroxidation, which in turn inhibits cancer cell growth and migration. However, delivery of naked siRNA remains a formidable challenge...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2018.101085
更新日期:2019-02-01 00:00:00
abstract::We previously reported that the highly reactive cell-free heme (CFH) is increased in the plasma of patients with chronic lung injury and causes pulmonary edema in animal model of acute respiratory distress syndrome (ARDS) post inhalation of halogen gas. However, the mechanisms by which CFH causes pulmonary edema are u...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2020.101592
更新日期:2020-09-01 00:00:00
abstract::Hypoxia triggers a wide range of protective responses in mammalian cells, which are mediated through transcriptional and post-translational mechanisms. Redox signaling in cells by reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) occurs through the reversible oxidation of cysteine thiol groups, resulting ...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2017.05.020
更新日期:2017-10-01 00:00:00
abstract::Despite extensive research that has been carried out over the past three decades in the field of renal ischaemia-reperfusion (I/R) injury, the pathogenic role of mitochondrial fission in renal I/R injury is poorly understood. The aim of our study is to investigate the molecular mechanism by which mammalian STE20-like ...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2018.10.012
更新日期:2019-01-01 00:00:00
abstract::Culturing cells and tissues in vitro has provided valuable insights into the molecular mechanisms regulating redox signaling in cells with implications for medicine. However, standard culture techniques maintain mammalian cells in vitro under an artificial physicochemical environment such as ambient air and 5% CO2. Ox...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2014.04.008
更新日期:2014-04-18 00:00:00
abstract::Cells employ multiple defence mechanisms to sustain a wide range of stress conditions associated with accumulation of modified self-biomolecules leading to lipo- and proteotoxicity. One of such mechanisms involves activation of the autophagy-lysosomal pathway for removal and degradation of modified lipids, proteins an...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101123
更新日期:2019-05-01 00:00:00
abstract::Hydroxytyrosol (HT) is a main phenolic component of olive oil. In this study, we investigated the safety and effects produced by HT purified (99.5%) from olive mill waste. HT was administered at a daily dosage of 45mg for 8 weeks to volunteers with mild hyperlipidemia (n=14). We measured markers of cardiovascular dise...
journal_title:Redox biology
pub_type: 临床试验,杂志文章
doi:10.1016/j.redox.2016.12.014
更新日期:2017-04-01 00:00:00
abstract::Glutathione peroxidase 2 (GPx2) is one of the five selenoprotein GPxs having a selenocysteine in the active center. GPx2 is strongly expressed in the gastrointestinal epithelium, as is another isoform, GPx1, though with a different localization pattern. Both GPxs are redox-active enzymes that are important for the red...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101388
更新日期:2020-01-01 00:00:00
abstract::Mitochondria are cellular energy powerhouses that play important roles in maintaining cell survival, cell death and cellular metabolic homeostasis. Timely removal of damaged mitochondria via autophagy (mitophagy) is thus critical for cellular homeostasis and function. Mitochondria are reticular organelles that have hi...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2014.11.006
更新日期:2015-01-01 00:00:00
abstract::Sulfane sulfur is common inside cells, playing both regulatory and antioxidant roles. However, there are unresolved issues about its chemistry and biochemistry. We report the discovery that reactive sulfane sulfur such as polysulfides and persulfides could be detected by using resonance synchronous spectroscopy (RS2)....
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101179
更新日期:2019-06-01 00:00:00
abstract::Oxidative stress plays a major part in the pathogenesis of drug-induced liver injury. Yet, overcoming it with other xenobiotics impose additional risks. In this study, we consider the use of natural-occurring and purified Vitamin E analogs as hepatoprotective agents. Vitamin E is well-known for its intrinsic antioxida...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2015.01.013
更新日期:2015-01-01 00:00:00
abstract::Oxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for f...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101181
更新日期:2019-06-01 00:00:00
abstract::Heart failure (HF) is the single largest cause for increased hospitalization after fine particulate matter (PM2.5) exposure. Patients with left HF often progress to right ventricular (RV) failure even with optimal medical care. An increase of PM2.5 of 10 μg per cubic meter was associated with a 76% increase in the ris...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101161
更新日期:2019-04-01 00:00:00
abstract::Obesity and excessive inflammation/oxidative stress are pathophysiological forces associated with kidney dysfunction. Although we recently showed that heme-oxygenase (HO) improves renal functions, the mechanisms are largely unclear. Moreover, the effects of the HO-system on podocyte cytoskeletal proteins like podocin,...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2014.09.001
更新日期:2014-01-01 00:00:00
abstract::Adropin, a secretory signal peptide, has shown beneficial effects on improving glucose homeostasis and dyslipidemia. However, whether this peptide affects nonalcoholic steatohepatitis (NASH) has remained unclear. In this study, the serum adropin levels, liver injury and oxidative stress were measured in diet-induced N...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2018.101068
更新日期:2019-02-01 00:00:00
abstract::In recent years, the gasotransmitter hydrogen sulphide (H2S), produced by the transsulphuration pathway, has been recognized as a biological mediator playing an important role under normal conditions and in various pathologies in both eukaryotes and prokaryotes. The transsulphuration pathway (TSP) includes the convers...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2020.101654
更新日期:2020-09-01 00:00:00
abstract::With the goal to enhance the distribution of cationic Mn porphyrins within mitochondria, the lipophilic Mn(III)meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, MnTnHex-2-PyP(5+) has been synthesized and tested in several different model of diseases, where it shows remarkable efficacy at as low as 50 µg/kg single or m...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2013.12.017
更新日期:2014-01-09 00:00:00
abstract::Hypertonia is pathognomonic of cerebral palsy (CP), often caused by brain injury before birth. To understand the early driving events of hypertonia, we utilized magnetic resonance imaging (MRI) assessment of early critical brain injury in rabbit fetuses (79% term) that will predict hypertonia after birth following ant...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101407
更新日期:2020-01-01 00:00:00
abstract::Glucose starvation is one of the major forms of metabolic stress in cancer cells. Deprivation of glucose impairs glycolysis and the pentose phosphate pathway, which elicits oxidative stress due to enhanced production of reactive oxygen species (ROS) and impaired antioxidant system, leading to redox imbalance and cell ...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2019.101154
更新日期:2019-07-01 00:00:00
abstract::Ischemia heart disease is the leading cause of death world-widely and has increased prevalence and exacerbated myocardial infarction with aging. Sestrin2, a stress-inducible protein, declines with aging in the heart and the rescue of Sestrin2 in the aged mouse heart improves the resistance to ischemic insults caused b...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2020.101556
更新日期:2020-07-01 00:00:00
abstract::The generation of NO by the various NO synthases in normal and malignant tissues is manifested by various biological effects that are involved in the regulation of cell survival, differentiation and cell death. The role of NO in the cytotoxic immune response was first revealed by demonstrating the induction of iNOS in...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2015.08.013
更新日期:2015-12-01 00:00:00
abstract::Metabolic control of cellular function is significant in the context of inflammation-induced metabolic dysregulation in immune cells. Generation of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide are one of the critical events that modulate the immune response in neutrophils. When activated, neu...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2016.06.003
更新日期:2016-10-01 00:00:00
abstract::Cells evolved robust homeostatic mechanisms to protect against oxidation or alkylation by electrophilic species. Glutathione (GSH) is the most abundant intracellular thiol, protects cellular components from oxidation and is maintained in a reduced state by glutathione reductase (GR). Nitro oleic acid (NO2-OA) is an el...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2018.11.008
更新日期:2019-02-01 00:00:00
abstract::Vitamin C deficiency globally affects several hundred million people and has been associated with increased morbidity and mortality in numerous studies. In this study, bioavailability of the oxidized form of vitamin C (l-dehydroascorbic acid or DHA)-commonly found in vitamin C containing food products prone to oxidati...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2015.11.003
更新日期:2016-04-01 00:00:00
abstract::Hydrogen peroxide (H2O2) at moderate steady-state concentrations synergizes with TNF-α, leading to increased nuclear levels of NF-κB p65 subunit and to a cell-type specific up-regulation of a limited number of NF-κB-dependent genes. Here, we address how H2O2 achieves this molecular specificity. HeLa and MCF-7 cells we...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2013.05.004
更新日期:2013-06-21 00:00:00
abstract::Hydrogen peroxide appears to be the key reactive oxygen species involved in redox signalling, but comparisons of the low concentrations of hydrogen peroxide that are calculated to exist within cells with those previously shown to activate common signalling events in vitro indicate that direct oxidation of key thiol gr...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2020.101484
更新日期:2020-08-01 00:00:00
abstract::Ischemia/reperfusion injury (I/R) is one of the leading causes of acute kidney injury (AKI) that typically occurs in renal surgeries. However, renal I/R still currently lacks effective therapeutic targets. In this study, we proved that inhibition of Brd4 with its selective inhibitor, JQ1, could exert a protective role...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101195
更新日期:2019-06-01 00:00:00
abstract::Emerging evidence suggests that oroxylin A exhibits antitumor effects by inducing cell apoptosis. However, the involved molecular mechanisms have not been elucidated. Here we report that the apoptosis induced by oroxylin A was dependent on p62-mediated activation of caspase-8 in hepatocellular carcinoma cells. Further...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101392
更新日期:2020-01-01 00:00:00
abstract::The biological functions of N6-methyladenosine (m6A) RNA methylation are mainly dependent on the reader; however, its role in lung tumorigenesis remains unclear. Here, we have demonstrated that the m6A reader YT521-B homology domain containing 2 (YTHDC2) is frequently suppressed in lung adenocarcinoma (LUAD). Downregu...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2020.101801
更新日期:2021-01-01 00:00:00