Mechanisms of Natural Food Dyes Curcumin on Regulation of HO-1/HO-2 and Inhibition of Aβ-Heme Compound in Alzheimer's Disease

2013 ◽  
Vol 781-784 ◽  
pp. 1148-1151 ◽  
Author(s):  
Xiong Zhang ◽  
Yang Lü ◽  
Jie Yun Sun ◽  
Yong Tang ◽  
Li Yu
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Dynamic Balance ◽  
Aging Brain ◽  
Natural Food ◽  
Key Factors ◽  
Food Dyes ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Underlying Mechanisms

More and more studies have reported that β-amyloid (Aβ)-induced oxidative stress and protein metabolism disorders along with their interactions are likely to be the key factors to the pathogenesis of Alzheimers disease (AD). Heme oxygenase (HO) is one member of stress responsive enzyme super family and is a joint of many hypothesis for AD, while oxidative stress, iron metabolism disorders and Aβ deposition are closely related with HO. Therefore, HO is expected to become a therapeutic target for AD. HO-1 and HO-2 are the main members of HO family, and keep dynamic balance. In normal aging brain tissues, the expression of HO-2 is high, and that of HO-1 is low; while in the cerebral cortex and hippocampus of AD patients, the expression of HO-1 is significantly increased. This phenomenon indicates that HO-1 has a protective effect to the neurons from the oxidative stress. Furthermore, heme and Aβ could form Aβ-heme compound, which is a peroxidase complex, which increase the oxidative damage to neurons. Recently, Curcumin has been shown cytoprotective properties by inducing HO-1 and by preventing the formation of Aβ-heme in neurons; however, the underlying mechanisms are still unclear to date. Therefore, there has been great interest in understanding the molecular mechanisms based on curcumin acts on.

scholarly journals Aging Brain: Prevention of Oxidative Stress by Vitamin E and Exercise

2009 ◽  
Vol 9 ◽  
pp. 366-372 ◽  
Author(s):  
Sambe Asha Devi
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Cognitive Decline ◽  
Middle Age ◽  
Neuronal Loss ◽  
Aging Brain ◽  
Key Factors ◽  
Esterase Inhibitors ◽  
The Brain ◽  
And Oxidative Stress

With aging, the brain undergoes neuronal loss in many areas. Although the loss of cells in the cerebral cortex, in particular the frontal cortex, has been recognized with aging, the influence of synaptic losses has a larger impact on cognitive decline. Much of the recent research on animals, as well as humans, has been aimed at slowing the cognitive decline through enrichment, and it has been found that the key factors are antioxidants and exercise. Several reports support the concept that regular supplementation of vitamin E and physical activity from as early as middle age can slow the cognitive decline observed during the later years. A few studies have also suggested that exercise is analogous to acetylcholine esterase inhibitors that are also used extensively to treat cognitive impairment and dementia in Alzheimer's disease. In addition, reports also support that vitamin E and exercise may act synergistically to overcome free radical injury and oxidative stress in the aging brain.

scholarly journals RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Konduru Seetharama Sastry ◽  
Haroon Naeem ◽  
Younes Mokrab ◽  
Aouatef Ismail Chouchane
Keyword(s):  
Oxidative Stress ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Late Phase ◽  
Global Gene Expression ◽  
Dependent Manner ◽  
Rna Seq ◽  
Notch Pathways ◽  
Underlying Mechanisms

Oxidative stress is known to induce melanocyte death, but the underlying mechanisms are incompletely understood. To identify oxidative stress-induced global gene expression changes in melanocytes, we treated PIG1 melanocytes with H2O2 in a dose- and time-dependent manner and performed RNA-seq. This approach allowed us to capture the events occurring early as well as late phase after treatment with H2O2. Our bioinformatics analysis identified differentially expressed genes involved in various biological processes of melanocytes which are known to contribute to the vitiligo development, such as apoptosis, autophagy, cell cycle regulation, cell adhesion, immune and inflammatory responses, melanocyte pluripotency, and developmental signaling such as WNT and NOTCH pathways. We uncovered several novel genes that are not previously described to be involved in melanocytic response to stress nor in vitiligo pathogenesis. Quantitative PCR and western blot analysis of selected proteins, performed on PIG1 and primary human epidermal melanocytes, confirmed the RNA-seq data. Interestingly, we discovered an aberrant regulation of several transcription factors that are involved in diabetes, neurological, and psychiatric diseases, all of which are comorbid conditions in patients with vitiligo. Our results may lead to a better understanding of the molecular mechanisms underlying vitiligo pathogenesis and help developing new drug targets for effective treatment.

scholarly journals Oxidative Stress in Intracerebral Hemorrhage: Sources, Mechanisms, and Therapeutic Targets

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Xin Hu ◽  
Chuanyuan Tao ◽  
Qi Gan ◽  
Jun Zheng ◽  
Hao Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Brain Damage ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Heme Iron ◽  
Mortality And Morbidity ◽  
Underlying Mechanisms ◽  
Damaging Effects

Intracerebral hemorrhage (ICH) is associated with the highest mortality and morbidity despite only constituting approximately 10–15% of all strokes. Complex underlying mechanisms consisting of cytotoxic, excitotoxic, and inflammatory effects of intraparenchymal blood are responsible for its highly damaging effects. Oxidative stress (OS) also plays an important role in brain injury after ICH but attracts less attention than other factors. Increasing evidence has demonstrated that the metabolite axis of hemoglobin-heme-iron is the key contributor to oxidative brain damage after ICH, although other factors, such as neuroinflammation and prooxidases, are involved. This review will discuss the sources, possible molecular mechanisms, and potential therapeutic targets of OS in ICH.

scholarly journals Responsive Expression of MafF to β-Amyloid-Induced Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xiaoxuan Wang ◽  
Yu Zhang ◽  
Xinkun Wan ◽  
Chenjia Guo ◽  
Jing Cui ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Leucine Zipper ◽  
Expression Patterns ◽  
Gene Expression Omnibus ◽  
Braak Stage ◽  
Specific Expression ◽  
Glutamate Cysteine Ligase ◽  
Intrahippocampal Injection ◽  
Amyloid Aβ ◽  
Β Amyloid

The small musculoaponeurotic fibrosarcoma (sMaf) proteins MafF, MafG, and MafK are basic region leucine zipper- (bZIP-) type transcription factors and display tissue- or stimulus-specific expression patterns. As the oxidative stress reactive proteins, sMafs are implicated in various neurological disorders. In the present study, the expressions of sMafs were investigated across five databases gathering transcriptomic data from 74 Alzheimer’s disease (AD) patients and 66 controls in the Gene Expression Omnibus (GEO) database. The expression of MafF was increased in the hippocampus of AD patients, which was negatively correlated with the expression of the glutamate cysteine ligase catalytic subunit (GCLC). Furthermore, MafF was significantly increased in patients with Braak stage V-VI, compared to those with Braak stage III-IV. β-Amyloid (Aβ), a strong inducer of oxidative stress, plays a crucial role in the pathogenesis of AD. The responsive expressions of sMafs to Aβ-induced oxidative stress were studied in the APP/PS1 mouse model of AD, Aβ intrahippocampal injection rats, and several human cell lines from different tissue origins. This study revealed that only the induction of MafF was accompanied with reduction of GCLC and glutathione (GSH). MafF knockdown suppressed the increase of GSH induced by Aβ. Among sMafs, MafF is the most responsive to Aβ-induced oxidative stress and might potentiate the inhibition of antioxidation. These results provide a better understanding of sMaf modulation in AD and highlight MafF as a potential therapeutic target in AD.

scholarly journals Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg?

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1479
Author(s):  
Elena Tamagno ◽  
Michela Guglielmotto ◽  
Valeria Vasciaveo ◽  
Massimo Tabaton
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangle ◽  
Metabolic Dysfunction ◽  
Antioxidant Treatment ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Ad Alzheimer’S Disease ◽  
Important Therapeutic Target

The pathogenesis of Alzheimer’s disease involves β amyloid (Aβ) accumulation known to induce synaptic dysfunction and neurodegeneration. The brain’s vulnerability to oxidative stress (OS) is considered a crucial detrimental factor in Alzheimer’s disease. OS and Aβ are linked to each other because Aβ induces OS, and OS increases the Aβ deposition. Thus, the answer to the question “which comes first: the chicken or the egg?” remains extremely difficult. In any case, the evidence for the primary occurrence of oxidative stress in AD is attractive. Thus, evidence indicates that a long period of gradual oxidative damage accumulation precedes and results in the appearance of clinical and pathological AD symptoms, including Aβ deposition, neurofibrillary tangle formation, metabolic dysfunction, and cognitive decline. Moreover, oxidative stress plays a crucial role in the pathogenesis of many risk factors for AD. Alzheimer’s disease begins many years before its symptoms, and antioxidant treatment can be an important therapeutic target for attacking the disease.

scholarly journals Macronutrient-Mediated Inflammation and Oxidative Stress: Relevance to Insulin Resistance, Obesity, and Atherogenesis

2019 ◽  
Vol 104 (12) ◽  
pp. 6118-6128 ◽  
Author(s):  
Fatimo Biobaku ◽  
Husam Ghanim ◽  
Manav Batra ◽  
Paresh Dandona
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Molecular Mechanisms ◽  
Evidence Synthesis ◽  
Caloric Intake ◽  
Inflammatory Stress ◽  
Insulin Signal Transduction ◽  
Dietary Choices ◽  
Proinflammatory Molecules ◽  
Underlying Mechanisms

Abstract Context The intake of macronutrients as components of a Western dietary pattern leads to oxidative stress and inflammation. Evidence Acquisition Data were largely retrieved from our previous and most recent work. PubMed and Google Scholar were searched for recent articles on the effect of macronutrients/dietary intake on inflammation, insulin resistance, obesity, and atherogenesis. The most relevant, high-quality articles were included in our review. Evidence Synthesis Our previous work has demonstrated the molecular mechanisms of macronutrient-mediated oxidative stress and inflammation. With the induction of inflammation, proinflammatory molecules potentially interfere with insulin signal transduction, thus causing insulin resistance. In addition, other molecules promote atherogenic inflammation. More recently, our work has also shown that certain foods are noninflammatory or anti-inflammatory and thus, do not interfere with insulin signaling. Finally, as obesity is induced by chronic excessive caloric intake, it is characterized by an increase in the expression of proinflammatory molecules, which are induced acutely by a Western diet. Caloric restriction, including fasting, is associated with a reduction in oxidative and inflammatory stress. Conclusions This review summarizes and attempts to provide an up-to-date profile of the molecular mechanisms involved in macronutrient-mediated oxidative/inflammatory stress and its potential consequences. An understanding of these underlying mechanisms is crucial for making appropriate dietary choices.

Evaluation of insulin resistance induced brain tissue dysfunction in obese dams and their neonates: Role of ipriflavone amelioration

2020 ◽  
Vol 23 ◽  
Author(s):  
Rania A. Gad ◽  
Eman S. Abdel-Reheim ◽  
Gaber M.G. Shehab ◽  
Hani S. Hafez ◽  
Abdelaziz S.A. Abuelsaad
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Superoxide Dismutase ◽  
Fatty Acid ◽  
Reduced Glutathione ◽  
Food Supplement ◽  
Natural Food ◽  
Β Amyloid ◽  
Anti Inflammatory

Background: Nonalcoholic steatohepatitis (NASH) is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. A high fat high cholesterol diet (HFD) was provided to female albino rats to establish a NASH model. It is well known that the offspring of obese mothers have an increased risk of obesity and diabetes. The present study aimed at evaluating the ameliorative effects of ipriflavone (IP) as a natural food supplement on the lipid metabolism, improving insulin sensitivity, reducing oxidative stress and inflammation, modifying metabolic risk factors and/or reduce brain damage, in both neonates and their dams. Materials and Methods: The present aim was achieved by evaluating the oxidative stress and antioxidant defense system biomarkers, as thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) activities. In addition, neurotransmitter acetylcholine (Ach) and acetylcholine esterase (AchE) activities, as well as levels of the apolipoprotein E4 (APOE4); β-secretase, hyper phosphor-tau and β-amyloid 42; 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG CoA R)” and COX-II by immunoblotting assays in the brain tissue of neonates and theirs dams in all the studied groups. Result: A very significant amelioration in acetylcholine and acetylcholine esterase neurotransmitters, Alzheimer’s makers (β-amyloid), antioxidants (reduced glutathione (GSH) contents, catalase (CAT) and superoxide dismutase (SOD); and inflammatory cytokines in NASH model is observed upon administrating ipriflavone (IP) as a natural food supplement. The multifunctional activities of ipriflavone as an antioxidant, anti-inflammatory and anti-insulin resistance drug were discussed and correlated with other investigations. Conclusion: Regarding steatohepatitis, the present study confirmed the anti-inflammatory effects of the ipriflavone (IP). Therefore, future studies should focus on hepatic fatty acid uptake, hepatic lipogenesis, and fatty acid oxidation and the role of IP in regulating hepatic fat metabolism. In addition, natural products like IP could be combined with the highly used pharmaceutical drugs to reduce the side effects of nonalcoholic steatohepatitis, and minimize progression of dementia. Moreover, present study supports further attempts to heal the neural dysfunction via antioxidant and anti-inflammatory cascade activities using ipriflavone (IP).

scholarly journals Linking Oxidative Stress and Proteinopathy in Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1231
Author(s):  
Chanchal Sharma ◽  
Sang Ryong Kim
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Changes ◽  
Aging Brain ◽  
Ros Production ◽  
Subsequent Loss ◽  
Β Amyloid ◽  
Neuroprotective Therapies

Proteinopathy and excessive production of reactive oxygen species (ROS), which are the principal features observed in the Alzheimer’s disease (AD) brain, contribute to neuronal toxicity. β-amyloid and tau are the primary proteins responsible for the proteinopathy (amyloidopathy and tauopathy, respectively) in AD, which depends on ROS production; these aggregates can also generate ROS. These mechanisms work in concert and reinforce each other to drive the pathology observed in the aging brain, which primarily involves oxidative stress (OS). This, in turn, triggers neurodegeneration due to the subsequent loss of synapses and neurons. Understanding these interactions may thus aid in the identification of potential neuroprotective therapies that could be clinically useful. Here, we review the role of β-amyloid and tau in the activation of ROS production. We then further discuss how free radicals can influence structural changes in key toxic intermediates and describe the putative mechanisms by which OS and oligomers cause neuronal death.

scholarly journals Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N6-Methyladenosine Modification

2021 ◽  
Vol 9 ◽  
Author(s):  
Yinghua Lv ◽  
Tianjiao Li ◽  
Manman Yang ◽  
Lihong Su ◽  
Zhendong Zhu ◽  
...  
Keyword(s):  
Reproductive System ◽  
Molecular Mechanisms ◽  
Dynamic Balance ◽  
Male Reproductive System ◽  
Ros Generation ◽  
Mitochondrial Dynamic ◽  
Chromium Vi ◽  
Underlying Mechanisms ◽  
Detoxification Process

Spermatogonial stem cells (SSCs) are the basis of spermatogenesis, and any damage to SSCs may result in spermatogenic disorder and male infertility. Chromium (Cr) (VI) is a proven toxin, mutagen, and carcinogen, perpetually detrimental to environmental organisms due to its intricate and enduring detoxification process in vivo. Despite this, the deleterious effects of Cr (VI) on SSCs and the underlying mechanisms remain poorly understood. In this study, we identified that Cr (VI) impaired male reproductive system in mouse testes and induced mitochondrial dynamic imbalance and mitophagy in SSCs/progenitors. Cr (VI) also downregulated the RNA N6-methyladenosine (m6A) modification levels in mitochondrial dynamic balance and mitophagy genes in SSCs/progenitors. Inspiringly, the toxic effects of Cr (VI) could be relieved by melatonin pretreatment. Melatonin alleviated Cr (VI)-induced damage to male reproductive system and autophagy in mouse testes. Melatonin also attenuated Cr (VI)-induced cell viability loss and reactive oxygen species (ROS) generation, as well as mitochondrial dynamic disorders and mitophagy in SSCs/progenitors. The protective roles of melatonin against Cr (VI)-induced mitophagy were exerted by restoration of METTL3-mediated RNA m6A modification and activation of mitochondrial fusion proteins MFN2 and OPA1, as well as inhibition of the mitophagy BNIP3/NIX receptor pathway. Thus, our study provides novel insights into the molecular mechanisms for RNA m6A modification underlying the gene regulatory network responsible for mitochondrial dynamic balance, and also lays new experimental groundwork for treatment of Cr (VI)-induced damage to male fertility.

scholarly journals Disrupted hippocampal growth hormone secretagogue receptor 1α interaction with dopamine receptor D1 plays a role in Alzheimer′s disease

2019 ◽  
Vol 11 (505) ◽  
pp. eaav6278 ◽  
Author(s):  
Jing Tian ◽  
Lan Guo ◽  
Shaomei Sui ◽  
Christopher Driskill ◽  
Aarron Phensy ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Dopamine Receptor ◽  
Molecular Mechanisms ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Simultaneous Application ◽  
Synaptic Physiology ◽  
Hippocampal Lesions ◽  
Amyloid Aβ ◽  
Β Amyloid

Hippocampal lesions are a defining pathology of Alzheimer’s disease (AD). However, the molecular mechanisms that underlie hippocampal synaptic injury in AD have not been fully elucidated. Current therapeutic efforts for AD treatment are not effective in correcting hippocampal synaptic deficits. Growth hormone secretagogue receptor 1α (GHSR1α) is critical for hippocampal synaptic physiology. Here, we report that GHSR1α interaction with β-amyloid (Aβ) suppresses GHSR1α activation, leading to compromised GHSR1α regulation of dopamine receptor D1 (DRD1) in the hippocampus from patients with AD. The simultaneous application of the selective GHSR1α agonist MK0677 with the selective DRD1 agonist SKF81297 rescued Ghsr1α function from Aβ inhibition, mitigating hippocampal synaptic injury and improving spatial memory in an AD mouse model. Our data reveal a mechanism of hippocampal vulnerability in AD and suggest that a combined activation of GHSR1α and DRD1 may be a promising approach for treating AD.

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