scholarly journals Prenatal and Postnatal Epigenetic Programming: Implications for GI, Immune, and Neuronal Function in Autism

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Mostafa I. Waly ◽  
Mady Hornig ◽  
Malav Trivedi ◽  
Nathaniel Hodgson ◽  
Radhika Kini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Capacity ◽  
Molecular Mechanisms ◽  
Excitatory Amino Acid ◽  
Regulation Of Gene Expression ◽  
Gi Tract ◽  
Excitatory Amino Acid Transporter ◽  
Epigenetic Programming ◽  
Genetic And Environmental Factors ◽  
Cysteine Uptake

Although autism is first and foremost a disorder of the central nervous system, comorbid dysfunction of the gastrointestinal (GI) and immune systems is common, suggesting that all three systems may be affected by common molecular mechanisms. Substantial systemic deficits in the antioxidant glutathione and its precursor, cysteine, have been documented in autism in association with oxidative stress and impaired methylation. DNA and histone methylation provide epigenetic regulation of gene expression during prenatal and postnatal development. Prenatal epigenetic programming (PrEP) can be affected by the maternal metabolic and nutritional environment, whereas postnatal epigenetic programming (PEP) importantly depends upon nutritional support provided through the GI tract. Cysteine absorption from the GI tract is a crucial determinant of antioxidant capacity, and systemic deficits of glutathione and cysteine in autism are likely to reflect impaired cysteine absorption. Excitatory amino acid transporter 3 (EAAT3) provides cysteine uptake for GI epithelial, neuronal, and immune cells, and its activity is decreased during oxidative stress. Based upon these observations, we propose that neurodevelopmental, GI, and immune aspects of autism each reflect manifestations of inadequate antioxidant capacity, secondary to impaired cysteine uptake by the GI tract. Genetic and environmental factors that adversely affect antioxidant capacity can disrupt PrEP and/or PEP, increasing vulnerability to autism.

scholarly journals Protective Role of Glutathione in the Hippocampus after Brain Ischemia

2021 ◽  
Vol 22 (15) ◽  
pp. 7765
Author(s):  
Youichirou Higashi ◽  
Takaaki Aratake ◽  
Takahiro Shimizu ◽  
Shogo Shimizu ◽  
Motoaki Saito
Keyword(s):  
Oxidative Stress ◽  
Neuronal Death ◽  
Excitatory Amino Acid ◽  
Ischemia Reperfusion ◽  
Thiol Group ◽  
Protective Role ◽  
Key Factor ◽  
Rate Limiting ◽  
Cysteine Uptake

Stroke is a major cause of death worldwide, leading to serious disability. Post-ischemic injury, especially in the cerebral ischemia-prone hippocampus, is a serious problem, as it contributes to vascular dementia. Many studies have shown that in the hippocampus, ischemia/reperfusion induces neuronal death through oxidative stress and neuronal zinc (Zn2+) dyshomeostasis. Glutathione (GSH) plays an important role in protecting neurons against oxidative stress as a major intracellular antioxidant. In addition, the thiol group of GSH can function as a principal Zn2+ chelator for the maintenance of Zn2+ homeostasis in neurons. These lines of evidence suggest that neuronal GSH levels could be a key factor in post-stroke neuronal survival. In neurons, excitatory amino acid carrier 1 (EAAC1) is involved in the influx of cysteine, and intracellular cysteine is the rate-limiting substrate for the synthesis of GSH. Recently, several studies have indicated that cysteine uptake through EAAC1 suppresses ischemia-induced neuronal death via the promotion of hippocampal GSH synthesis in ischemic animal models. In this article, we aimed to review and describe the role of GSH in hippocampal neuroprotection after ischemia/reperfusion, focusing on EAAC1.

scholarly journals Oxidative Stress in Myopia

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Bosch-Morell Francisco ◽  
Mérida Salvador ◽  
Navea Amparo
Keyword(s):  
Oxidative Stress ◽  
Retinal Detachment ◽  
High Myopia ◽  
Molecular Mechanisms ◽  
Medical Problem ◽  
Regulatory Pathways ◽  
Eye Growth ◽  
Genetic And Environmental Factors ◽  
The One ◽  
Macular Hemorrhage

Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem.

scholarly journals Neuregulin-1 Inhibits CoCl2-Induced Excitatory Amino Acid Carrier 1 Overexpression and Oxidative Stress in SH-SY5Y Cells

2020 ◽  
Author(s):  
Han-Byeol Kim ◽  
Ji-Young Yoo ◽  
Seung-Yeon Yoo ◽  
Jun-Ho Lee ◽  
Hye-Sun Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Protective Role ◽  
Amino Acid Transporters ◽  
Dependent Manner ◽  
Neuregulin 1 ◽  
Induced Apoptosis ◽  
Cysteine Uptake ◽  
Amino Acid Carrier

Abstract Excitatory amino acid carrier 1 (EAAC1) is an important subtype of excitatory amino acid transporters (EAATs) and is the route for neuronal cysteine uptake. CoCl2 is not only a hypoxia-mimetic reagent but also an oxidative stress inducer. Here, we found that CoCl2 induced significant overexpression of EAAC1 in a dose- and time-dependent manner. We further demonstrated that pretreatment with NRG1 rescued the CoCl2-induced upregulation of EAAC1 and tau expression. Neuregulin-1 (NRG1) plays a protective role in the CoCl2-induced accumulation of reactive oxygen species (ROS) and reduction in antioxidative enzyme (SOD and Gpx) activity. Moreover, NRG1 attenuated CoCl2-induced apoptosis and cell death. NRG1 inhibited the CoCl2-induced release of cleaved caspase-3 and reduction in Bcl-XL. Our novel findings suggest that NRG1 may play a protective role in oxidative stress and hypoxia through the regulation of EAAC1.

Pleiotropic roles of melatonin against oxidative stress mediated tissue injury in the gastrointestinal tract: An overview

2019 ◽  
Vol 2 (2) ◽  
pp. 158-184 ◽  
Author(s):  
Palash K Pal ◽  
Bharati Bhattacharjee ◽  
Aindrila Chattopadhyay ◽  
Debasish Bandyopadhyay
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Gi Tract ◽  
Pathological Conditions

The excessive production of free radicals and/or reactive oxygen species (ROS) in gastrointestinal (GI) tract leads to oxidative damages in GI tissues with development of varied pathological conditions and clinical symptoms. Many endogenous as well as exogenous factors are involved in such pathogenesis, herein, focus was given to the factors of metal toxicity, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion, consumption of high fat diet and alcohol, and different pathological conditions and diseases. Since ROS is more or less involved in the GI damages caused by these factors, therefore attempts have been made to develop appropriate therapeutic agents that possess antioxidant properties. Being a potent antioxidant and free radical scavenger, melatonin was suggested as a potent therapeutic answer to these GI damages. The discovery of different binding sites and receptors of melatonin in the GI tissues further proves its local actions to protect these tissues from oxidative stress.  In the review, we attempt to try our best to summarize the current developments regarding the GI injuries caused by oxidative stress and the potential beneficial effects of melatonin on these injuries. The important molecular mechanisms associated with these changes were also highlighted in the discussion. We hope that this review will provide valuable information to consider melatonin as a suitable molecule used for GI tract protection.

Research on the Relationship Between Schizophrenia and Excitatory Amino Acid Transporter 1 Gene Based on Nanogold Amplification Technology

2021 ◽  
Vol 21 (2) ◽  
pp. 1278-1285
Author(s):  
Shuang Zheng ◽  
Wen Xie ◽  
Longcai Fei ◽  
Nannan Zhu
Keyword(s):  
Candidate Gene ◽  
Excitatory Amino Acid ◽  
Susceptibility Gene ◽  
Detection Sensitivity ◽  
Excitatory Amino Acid Transporter ◽  
Gene Recognition ◽  
Nano Gold ◽  
Candidate Gene Association ◽  
Genetic And Environmental Factors ◽  
The Relationship

Schizophrenia is one of the most common central nervous system diseases, which is caused by abnormal discharge of neurons in the brain. Its occurrence and development are affected by both genetic and environmental factors. The variation of gene level can affect the development of schizophrenia and the treatment of prognosis by affecting the susceptibility, clinical phenotype and drug response. At present, the research results of susceptibility genes screened by candidate gene association research are not consistent. The method of gene recognition on DNA was studied by QCM and nano gold composite. By using this method, the enantioselective recognition of cysteine on cyclodextrin self-assembled membrane was studied. In this study, EAAT1 gene, which is highly expressed in astrocytes, was used as a candidate gene to analyze the relationship between polymorphism and schizophrenia. The experimental results show that the introduction of nano gold can significantly improve the sensing signal, detection sensitivity and gene differentiation. In addition, this study suggested that EAAT1 gene might be a susceptibility gene of schizophrenia in the population. The results showed that a common SNP allele rs1030239-g was the risk factor (83.8% vs. 79.2%, P = 0.00067, or = 1.35, 95% CI = 1.08-1.69). The results showed that A-T-G increased the risk of schizophrenia.

scholarly journals Evaluation of Waste Mushroom Compost as a Feed Supplement and Its Effects on the Fat Metabolism and Antioxidant Capacity of Broilers

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 445 ◽  
Author(s):  
Wen Yang Chuang ◽  
Chu Ling Liu ◽  
Chia Fen Tsai ◽  
Wei Chih Lin ◽  
Shen Chang Chang ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Excitatory Amino Acid ◽  
Pennisetum Purpureum ◽  
Related Factor ◽  
Feed Conversion ◽  
Feed Supplement ◽  
Mushroom Compost ◽  
Excitatory Amino Acid Transporter ◽  
Treatment Groups ◽  
Ifn Γ

Pennisetum purpureum Schum No. 2 waste mushroom compost (PWMC) is the main byproduct when cultivating Pleurotus eryngii. Due to the high mycelium levels in PWMC, it may have potential as a feed supplement for broilers. This study investigated the effects of PWMC supplementation on antioxidant capacity and adipose metabolism in broilers. In the study, 240 broilers were randomly allocated to one of four treatment groups: basal diet (control), 0.5%, 1%, or 2% PWMC supplementation. Each treatment group had 60 broilers, divided into three replicates. The results showed that supplementation with 0.5% PWMC decreased the feed conversion rate (FCR) from 1.36 to 1.28, compared to the control. Supplementation with 0.5% or 2% PWMC decreased glucose and triglyceride levels, compared to the control (p < 0.0001), the concentrations of adiponectin and oxytocin increased from 5948 to 5709, 11820, and 7938 ng/ mL; and 259 to 447, 873, and 963 pg/ mL, respectively. Toll-like receptor 4 was slightly increased in the 0.5% and 1% PWMC groups. Both interferon-γ (IFN-γ) and interleukin-1ß (IL-1ß) were significantly decreased, by about three to five times for IFN-γ (p < 0.0001) and 1.1 to 1.6 times for IL-1ß (p = 0.0002). All antioxidant-related mRNA, including nuclear factor erythroid 2–related factor 2 (Nrf-2) and superoxidase dismutase-1 (SOD-1), increased significantly following PWMC supplementation. Both claudin-1 and zonula occludens 1 increased, especially in the 2% PWMC group. Excitatory amino acid transporter 3 (EAAT3) significantly increased by about 5, 12, and 11 times in the 0.5%, 1%, and 2% PWMC groups. All adipolysis-related mRNA were induced in the PWMC treatment groups, further enhancing adipolysis. Overall, 0.5% PWMC supplementation was recommended due to its improving FCR, similar antioxidant capacity, and upregulated adipolysis.

scholarly journals Neuregulin 1 Promotes Glutathione-Dependent Neuronal Cobalamin Metabolism by Stimulating Cysteine Uptake

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yiting Zhang ◽  
Nathaniel Hodgson ◽  
Malav Trivedi ◽  
Richard Deth
Keyword(s):  
Energy Homeostasis ◽  
Excitatory Amino Acid ◽  
Neuroblastoma Cells ◽  
Vitamin B ◽  
Human Neuroblastoma Cells ◽  
Excitatory Amino Acid Transporter ◽  
Human Neuroblastoma ◽  
Neuregulin 1 ◽  
Cobalamin Metabolism ◽  
Cysteine Uptake

Neuregulin 1 (NRG-1) is a key neurotrophic factor involved in energy homeostasis and CNS development, and impaired NRG-1 signaling is associated with neurological disorders. Cobalamin (Cbl), also known as vitamin B12, is an essential micronutrient which mammals must acquire through diet, and neurologic dysfunction is a primary clinical manifestation of Cbl deficiency. Here we show that NRG-1 stimulates synthesis of the two bioactive Cbl species adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl) in human neuroblastoma cells by both promoting conversion of inactive to active Cbl species and increasing neuronal Cbl uptake. Formation of active Cbls is glutathione- (GSH-) dependent and the NRG-1-initiated increase is dependent upon its stimulation of cysteine uptake by excitatory amino acid transporter 3 (EAAT3), leading to increased GSH. The stimulatory effect of NRG-1 on cellular Cbl uptake is associated with increased expression of megalin, which is known to facilitate Cbl transport in ileum and kidney. MeCbl is a required cofactor for methionine synthase (MS) and we demonstrate the ability of NRG-1 to increase MS activity, and affect levels of methionine methylation cycle metabolites. Our results identify novel neuroprotective roles of NRG-1 including stimulating antioxidant synthesis and promoting active Cbl formation.

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