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

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.

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Characteristics and Expression Pattern of MYC Genes in Triticum aestivum, Oryza sativa, and Brachypodium distachyon

Plants ◽

10.3390/plants8080274 ◽

2019 ◽

Vol 8 (8) ◽

pp. 274 ◽

Cited By ~ 2

Author(s):

Shoukun Chen ◽

Hongyan Zhao ◽

Tengli Luo ◽

Yue Liu ◽

Xiaojun Nie ◽

...

Keyword(s):

Transcriptional Activation ◽

Leucine Zipper ◽

Brachypodium Distachyon ◽

Expression Patterns ◽

Terminal Region ◽

Gene Promoters ◽

Interaction Domain ◽

Specific Expression ◽

Systematic Analysis ◽

Transcriptional Activation Domain

Myelocytomatosis oncogenes (MYC) transcription factors (TFs) belong to basic helix-loop-helix (bHLH) TF family and have a special bHLH_MYC_N domain in the N-terminal region. Presently, there is no detailed and systematic analysis of MYC TFs in wheat, rice, and Brachypodium distachyon. In this study, 26 TaMYC, 7 OsMYC, and 7 BdMYC TFs were identified and their features were characterized. Firstly, they contain a JAZ interaction domain (JID) and a putative transcriptional activation domain (TAD) in the bHLH_MYC_N region and a BhlH region in the C-terminal region. In some cases, the bHLH region is followed by a leucine zipper region; secondly, they display tissue-specific expression patterns: wheat MYC genes are mainly expressed in leaves, rice MYC genes are highly expressed in stems, and B. distachyon MYC genes are mainly expressed in inflorescences. In addition, three types of cis-elements, including plant development/growth-related, hormone-related, and abiotic stresses-related were identified in different MYC gene promoters. In combination with the previous studies, these results indicate that MYC TFs mainly function in growth and development, as well as in response to stresses. This study laid a foundation for the further functional elucidation of MYC genes.

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

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.781-784.1148 ◽

2013 ◽

Vol 781-784 ◽

pp. 1148-1151 ◽

Cited By ~ 1

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.

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Lactobacilli and bifidobacteria ameliorate memory and learning deficits and oxidative stress in β-amyloid (1–42) injected rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2017-0648 ◽

2018 ◽

Vol 43 (7) ◽

pp. 718-726 ◽

Cited By ~ 49

Author(s):

Somayeh Athari Nik Azm ◽

Abolghassem Djazayeri ◽

Majid Safa ◽

Kian Azami ◽

Behzad Ahmadvand ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Morris Water Maze ◽

Water Maze ◽

Oxidative Stress Biomarkers ◽

Memory And Learning ◽

Stress Biomarkers ◽

Intrahippocampal Injection ◽

Β Amyloid ◽

And Oxidative Stress

The gastrointestinal microbiota affects brain function, including memory and learning. In this study we investigated the effects of probiotics on memory and oxidative stress biomarkers in an experimental model of Alzheimer’s disease. Sixty rats were randomly divided into 5 groups: control; control-probiotics, which received probiotics for 8 weeks; sham operation, which received an intrahippocampal injection of phosphate-buffered saline; Alzheimer, which received an intrahippocampal injection of β-amyloid (Aβ1–42); and Alzheimer-probiotics, which in addition to being injected with Aβ1–42, received 2 g (1 × 1010 CFU/g) of probiotics (Lactobacillus acidophilus, L. fermentum, Bifidobacterium lactis, and B. longum) for 8 weeks. Memory and learning were measured using the Morris water maze, and oxidative stress biomarkers in the hippocampus were measured using ELISA kits. Morris water maze results indicated that compared with the Alzheimer group, the Alzheimer-probiotics group had significantly improved spatial memory, including shorter escape latency and travelled distance and greater time spent in the target quadrant. There was also improvement in oxidative stress biomarkers such as increased malondialdehyde levels and superoxide dismutase activity following the β-amyloid injection. Overall, it seems that probiotics play a role in improving memory deficit and inhibiting the pathological mechanisms of Alzheimer’s disease by modifying microbiota.

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

Antioxidants ◽

10.3390/antiox10091479 ◽

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.

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Bioinformatic prediction of upstream microRNAs of PPO and novel microRNAs in potato

Canadian Journal of Plant Science ◽

10.4141/cjps-2014-308 ◽

2015 ◽

Vol 95 (5) ◽

pp. 871-877 ◽

Cited By ~ 5

Author(s):

Ming Chi ◽

Chimin Liu ◽

Yinquan Su ◽

Yongwei Tong ◽

Hanyun Liu

Keyword(s):

Small Rna ◽

Stress Responses ◽

Gene Prediction ◽

Expression Patterns ◽

Gene Expression Omnibus ◽

Brown Spot ◽

Sequencing Data ◽

Tuber Tissue ◽

Specific Expression ◽

Encoding Genes

Chi, M., Liu, C., Su, Y., Tong, Y. and Liu, H. 2015. Bioinformatic prediction of upstream microRNAs of PPO and novel microRNAs in potato. Can. J. Plant Sci. 95: 871–877. MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that play roles in many biological processes of plants. This study aimed to identify novel miRNAs and miRNAs targeting polyphenol oxidase (PPO) in potato. Small RNA-seq data (GSE32471 and GSE52599) including sequencing data of flower, leaf, stem, root, stolon and tuber tissue of potato were downloaded from Gene Expression Omnibus. After quality control and data cleaning of the raw data, the clean data were then mapped to Rfam to screen the reads corresponding to miRNA rather than other types of small RNA by Bowtie. Furthermore, the screened high-quality reads were mapped to known miRNAs in miRBase to identify and predict the novel miRNAs by miRDeep2. Finally, target gene prediction was performed for all identified miRNAs using psRNATarget and their roles in stress responses and brown spot of potato tubers through PPO genes were analyzed. A total of 18 novel potato miRNAs were identified and all of them had their specific expression patterns in different tissues. Targets prediction showed that some novel miRNAs (e.g., ST4.03ch03_9018, ST4.03ch05_15199 and ST4.03ch11_31208) could regulate the expression of potato resistance genes. Moreover, eight known miRNAs were found to target 3 PPO encoding genes, while they expressed at a low level in tuber tissue. Novel miRNAs might be associated with stress resistance of potato, and upstream miRNAs of PPO encoding genes might be important in suppression of potato brown spot.

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β-Asarone Ameliorates β-Amyloid–Induced Neurotoxicity in PC12 Cells by Activating P13K/Akt/Nrf2 Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.659955 ◽

2021 ◽

Vol 12 ◽

Author(s):

Miaomiao Meng ◽

Lijuan Zhang ◽

Di AI ◽

Hongyun Wu ◽

Wei Peng

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Neuronal Damage ◽

Cell Model ◽

Cell Damage ◽

Neuroprotective Effects ◽

Akt Phosphorylation ◽

Nrf2 Signaling Pathway ◽

Amyloid Aβ ◽

Β Amyloid

Accumulation of β-amyloid (Aβ) causes oxidative stress, which is the major pathological mechanism in Alzheimer’s disease (AD). β-asarone could reduce Aβ-induced oxidative stress and neuronal damage, but the molecular mechanism remains elusive. In this study, we used an Aβ-stimulated PC12 cell model to explore the neuroprotective effects and potential mechanisms of β-asarone. The results showed that β-asarone could improve cell viability and weaken cell damage and apoptosis. β-asarone could also decrease the level of ROS and MDA; increase the level of SOD, CAT, and GSH-PX; and ameliorate the mitochondrial membrane potential. Furthermore, β-asarone could promote the expression of Nrf2 and HO-1 by upregulating the level of PI3K/Akt phosphorylation. In conclusion, β-asarone could exert neuroprotective effects by modulating the P13K/Akt/Nrf2 signaling pathway. β-asarone might be a promising therapy for AD.

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Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents

Marine Drugs ◽

10.3390/md20010075 ◽

2022 ◽

Vol 20 (1) ◽

pp. 75

Author(s):

Elisabete Lima ◽

Jorge Medeiros

Keyword(s):

Oxidative Stress ◽

Complex Disease ◽

Marine Organisms ◽

Neuroprotective Effects ◽

Amyloid Aβ ◽

Β Amyloid ◽

Amino Acid Tryptophan ◽

Τ Protein ◽

Derivatives Of ◽

Neuron Apoptosis

The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), increases continuously demanding the urgent development of anti-Alzheimer’s agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, such as akaloids, to defend themselves. Therefore, the identification of marine natural products with neuroprotective effects is a necessity. Being that AD is not only a genetic but also an environmental complex disease, a treatment for AD remains to discover. As the major clinical indications (CI) of AD are extracellular plaques formed by β-amyloid (Aβ) protein, intracellular neurofibrillary tangles (NFTs) formed by hyper phosphorylated τ-protein, uncommon inflammatory response and neuron apoptosis and death caused by oxidative stress, alkaloids that may decrease CI, might be used against AD. Most of the alkalolids with those properties are derivatives of the amino acid tryptophan mainly with a planar indole scaffold. Certainly, alkaloids targeting more than one CI, multitarget-directed ligands (MTDL), have the potential to become a lead in AD treatment. Alkaloids to have a maximum of activity against CI, should be planar and contain halogens and amine quaternization.

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Genome-Wide Identification ofbZIPFamily Genes Involved in Drought and Heat Stresses in Strawberry (Fragaria vesca)

International Journal of Genomics ◽

10.1155/2017/3981031 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 7

Author(s):

Xiao-Long Wang ◽

Xinlu Chen ◽

Tian-Bao Yang ◽

Qunkang Cheng ◽

Zong-Ming Cheng

Keyword(s):

Leucine Zipper ◽

Developmental Stages ◽

Expression Patterns ◽

Normal Growth ◽

Growth Conditions ◽

Fragaria Vesca ◽

Basic Leucine Zipper ◽

Specific Expression ◽

Weak Expression ◽

Bzip Proteins

Basic leucine zipper (bZIP) genes are known to play a crucial role in response to various processes in plant as well as abiotic or biotic stress challenges. We have performed an identification and characterization of 50bZIPgenes across the woodland strawberry (Fragaria vesca) genome, which were divided into 10 clades according to the phylogenetic relationship of the strawberry bZIP proteins with those inArabidopsisand rice. Five categories of intron patterns were observed within basic and hinge regions of the bZIP domains. Some additional conserved motifs have been found with the group specificity. Further, we predicted DNA-binding specificity of the basic and hinge regions as well as dimerization properties of leucine zipper regions, which was consistent with our phylogenetic clade and classified into 20 subfamilies. Across the different developmental stages of 15 organs and two types of fruits, the clade AbZIPmembers showed different tissue-specific expression patterns and the duplicated genes were differentially regulated, indicating a functional diversification coupled with the expansion of this gene family in strawberry. Under normal growth conditions,mrna11837andmrna30280of clade A showed very weak expression levels in organs and fruits, respectively; but higher expression was observed with different set of genes following drought and heat treatment, which may be caused by the separate response pathway between drought and heat treatments.

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Tissue-specific expression patterns of nuclear receptors

NURSA Datasets ◽

10.1621/datasets.02001 ◽

2013 ◽

Author(s):

AL Bookout ◽

Y Jeong ◽

M Downes ◽

RT Yu ◽

RM Evans ◽

...

Keyword(s):

Nuclear Receptors ◽

Expression Patterns ◽

Specific Expression ◽

Tissue Specific ◽

Tissue Specific Expression

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Amentoflavone: A Bifunctional Metal Chelator that Controls the Formation of Neurotoxic Soluble Aβ42 Oligomers

10.26434/chemrxiv.12445505 ◽

2020 ◽

Author(s):

Liang Sun ◽

Anuj K. Sharma ◽

Byung-Hee Han ◽

Liviu M. Mirica

Keyword(s):

Reactive Oxygen Species ◽

Metal Ions ◽

Antioxidant Properties ◽

Reactive Oxygen ◽

Amyloid Plaques ◽

Transition Metal Ions ◽

Oxygen Species ◽

High Affinity ◽

Amyloid Aβ ◽

Β Amyloid

Alzheimer's disease (AD) is the most common neurodegenerative disorder, yet the cause and progression of this disorder are not completely understood. While the main hallmark of AD is the deposition of amyloid plaques consisting of the β-amyloid (Aβ) peptide, transition metal ions are also known to play a significant role in disease pathology by expediting the formation of neurotoxic soluble β-amyloid (Aβ) oligomers, reactive oxygen species (ROS), and oxidative stress. Thus, bifunctional metal chelators that can control these deleterious properties are highly desirable. Herein, we show that amentoflavone (AMF) – a natural biflavonoid compound, exhibits good metal-chelating properties, especially for chelating Cu2+ with very high affinity (pCu7.4 = 10.44). In addition, AMF binds to Aβ fibrils with a high affinity (Ki = 287 ± 20 nM) – as revealed by a competition thioflavin T (ThT) assay, and specifically labels the amyloid plaques ex vivo in the brain sections of transgenic AD mice – as confirmed via immunostaining with an Ab antibody. The effect of AMF on Aβ42 aggregation and disaggregation of Aβ42 fibrils was also investigated, to reveal that AMF can control the formation of neurotoxic soluble Aβ42 oligomers, both in absence and presence of metal ions, and as confirmed via cell toxicity studies. Furthermore, an ascorbate consumption assay shows that AMF exhibits potent antioxidant properties and can chelate Cu2+ and significantly diminish the Cu2+-ascorbate redox cycling and reactive oxygen species (ROS) formation. Overall, these studies strongly suggest that AMF acts as a bifunctional chelator that can interact with various Aβ aggregates and reduce their neurotoxicity, can also bind Cu2+ and mediate its deleterious redox properties, and thus AMF has the potential to be a lead compound for further therapeutic agent development for AD.

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