MicroRNA-98 reduces amyloid β-protein production and improves oxidative stress and mitochondrial dysfunction through the Notch signaling pathway via HEY2 in Alzheimer's disease mice.

Abstract:

:Alzheimer's disease (AD) is a chronic neurodegenerative disease that often occurs at a slow pace yet deteriorates with time. MicroRNAs (miRs) have been demonstrated to offer novel therapeutic hope for disease treatment. The aim of the present study was to investigate the effect of miR‑98 on amyloid β (Aβ)‑protein production, oxidative stress and mitochondrial dysfunction through the Notch signaling pathway by targeting hairy and enhancer of split (Hes)‑related with YRPW motif protein 2 (HEY2) in mice with AD. A total of 70 Kunming mice were obtained and subjected to behavioral assessment. The levels of oxidative stress‑related proteins glutathione peroxidase, reduced glutathione, superoxide dismutase, malondialdehyde, acetylcholinesterase and Na+‑K+‑ATP were measured. Morphological changes in brain tissue, HEY2‑positivity levels, neuronal apoptotic index (AI) and neuron mitochondrial DNA (mtDNA) levels were also determined. Subsequently, the levels of miR‑98 and the mRNA and protein levels of HEY2, Jagged1, Notch1, Hes1, Hes5, β‑amyloid precursor protein, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein in tissues and hippocampal neurons were determined by reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. Finally, hippocampal neuron viability and apoptosis were determined using an MTT assay and flow cytometry, respectively. The levels of miR‑98‑targeted HEY2 and miR‑98 were low and the levels of HEY2 were high in the AD mice. The AD mice exhibited poorer learning and memory abilities, oxidative stress function, and morphological changes of pyramidal cells in the hippocampal CA1 region. Furthermore, the AD mice exhibited increased protein levels of HEY2 and AI in the CA1 region of brain tissues with reduced mtDNA levels and dysfunctional neuronal mitochondria. miR‑98 suppressed hippocampal neuron apoptosis and promoted hippocampal neuron viability by inactivating the Notch signaling pathway via the inhibition of HEY2. In conclusion, the results demonstrated that miR‑98 reduced the production of Aβ and improved oxidative stress and mitochondrial dysfunction through activation of the Notch signaling pathway by binding to HEY2 in AD mice.

journal_name

Int J Mol Med

authors

Chen FZ,Zhao Y,Chen HZ

doi

10.3892/ijmm.2018.3957

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

91-102

issue

1

eissn

1107-3756

issn

1791-244X

journal_volume

43

pub_type

杂志文章
  • Ectromelia virus upregulates the expression of heat shock protein 70 to promote viral replication.

    abstract::The ectromelia virus (ECTV) is a mouse specific Orthopoxvirus that causes lethal infection in some mouse strains. ECTV infection of these mouse strains has been used as a valuable model for understanding the interplay between Orthopoxvirus species and their hosts, including variola virus in humans. Although poxviruses...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3655

    authors: Cheng W,Jia H,Wang X,He X,Jin Q,Cao J,Jing Z

    更新日期:2018-08-01 00:00:00

  • Influence of stannous chloride on the adhesive properties of Corynebacterium diphtheriae strains.

    abstract::Stannous ion, as a chloride salt, influenced on the survival and adhesive properties of two toxigenic Corynebacterium diphtheriae of the sucrose-fermenting (241 strain) and non-sucrose-fermenting (CDC-E8392 strain) biotypes. Differences in survival fractions suggested differences in susceptibility of strains to bacter...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Silva De Souza SM,Hirata R Jr,Moreira LO,Gomes ML,Braga De Andrade AF,Bernardo-Filho M,Mattos-Guaraldi AL

    更新日期:2003-10-01 00:00:00

  • Galectin-9 as a regulator of cellular adhesion in human oral squamous cell carcinoma cell lines.

    abstract::Oral squamous cell carcinomas (OSCCs), a major public health problem worldwide, are the most common neoplasms of the head and neck. The most important prognostic indicator for patients with OSCC is metastasis to cervical lymph nodes or distant organs. Galectin-9 is correlated with cellular adhesion and aggregation in ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Kasamatsu A,Uzawa K,Nakashima D,Koike H,Shiiba M,Bukawa H,Yokoe H,Tanzawa H

    更新日期:2005-08-01 00:00:00

  • miR‑93‑5p regulates the occurrence and development of esophageal carcinoma epithelial cells by targeting TGFβR2.

    abstract::Emerging studies have indicated that the dysregulation of microRNAs (miRNAs or miRs) plays a vital role in the development and metastasis of tumors. However, the role of miR‑93‑5p in esophageal carcinoma (EC) has not been extensively reported. The present study thus focused on the role of miR‑93‑5p and its downstream ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2020.4836

    authors: Cai Y,Ruan W,Ding J,Wei N,Wang J,Zhang H,Ma N,Weng G,Su WK,Lin Y,Zhu K

    更新日期:2021-03-01 00:00:00

  • FSH1 regulates the phenotype and pathogenicity of the pathogenic dermatophyte Microsporum canis.

    abstract::Microsporum canis (M. canis) is a common pathogen that causes tinea capitis and is present worldwide. The incidence of M. canis infection, particularly tinea capitis, has been increasing in China. In our previous studies, family of serine hydrolases 1 (FSH1) was identified as a potential virulence factor in tinea capi...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2019.4355

    authors: Zhang F,Tan C,Xu Y,Yang G

    更新日期:2019-12-01 00:00:00

  • [Corrigendum] Heat shock protein 90/Akt pathway participates in the cardioprotective effect of exogenous hydrogen sulfide against high glucose‑induced injury to H9c2 cells.

    abstract::Subsequently to the publication of this article, the authors have realized that the address affiliation for the corresponding author, Chengheng Hu, and the authors Longyun Peng and Xinxue Liao appeared incorrectly. These authors' affiliation information should have appeared as follows (the corrected address affiliatio...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3708

    authors: Ke X,Chen J,Peng L,Zhang W,Yang Y,Liao X,Mo L,Guo R,Feng J,Hu C,Nie R

    更新日期:2018-09-01 00:00:00

  • Ghrelin, an endogenous ligand for the growth hormone-secretagogue receptor, is expressed in the human adrenal cortex.

    abstract::Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), which was originally isolated from rat stomach. Ghrelin and GHS-R are also expressed in several peripheral tissues, including adrenal glands, and this prompted us to study ghrelin expression and ghrelin-binding site localization in th...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Tortorella C,Macchi C,Spinazzi R,Malendowicz LK,Trejter M,Nussdorfer GG

    更新日期:2003-08-01 00:00:00

  • Decreased expression of claudin-1 correlates with recurrence status in breast cancer.

    abstract::Claudins (CLDNs) constitute the major transmembrane proteins of tight junctions. It may be hypothesized that changes in or loss of expression of tight junctional proteins such as CLDNs can lead to cellular disorientation and detachment, which is commonly seen in neoplasia. Recent studies have suggested that claudin-1 ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Morohashi S,Kusumi T,Sato F,Odagiri H,Chiba H,Yoshihara S,Hakamada K,Sasaki M,Kijima H

    更新日期:2007-08-01 00:00:00

  • Caffeic acid phenethyl ester reduces the secretion of vascular endothelial growth factor through the inhibition of the ROS, PI3K and HIF-1α signaling pathways in human retinal pigment epithelial cells under hypoxic conditions.

    abstract::Choroidal neovascularization (CNV) can lead to progressive and severe visual loss. Vascular endothelial growth factor (VEGF) promotes the development of CNV. Caffeic acid phenethyl ester (CAPE), a biologically active component of the honeybee (Apis mellifera) propolis, has been demonstrated to have several interesting...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2015.2116

    authors: Paeng SH,Jung WK,Park WS,Lee DS,Kim GY,Choi YH,Seo SK,Jang WH,Choi JS,Lee YM,Park S,Choi IW

    更新日期:2015-05-01 00:00:00

  • Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

    abstract::Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and con...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2012.1164

    authors: Bianchi E,Scarinci F,Ripandelli G,Feher J,Pacella E,Magliulo G,Gabrieli CB,Plateroti R,Plateroti P,Mignini F,Artico M

    更新日期:2013-01-01 00:00:00

  • Correlation of PU.1 and signal regulatory protein α1 expression in PU.1 transgenic K562 cells.

    abstract::PU.1 is a key transcription factor for hematopoiesis and the reduction of this protein expression plays important roles in various hematological malignancies. To identify PU.1 downstream target genes, we recently reported dual microarray analyses, using PU.1 knockdown K562 (K562PU.1...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2011.827

    authors: Iseki Y,Nakahara M,Kubo M,Obata F,Harigae H,Takahashi S

    更新日期:2012-02-01 00:00:00

  • Circular RNA CSNK1G1 promotes the progression of osteoarthritis by targeting the miR‑4428/FUT2 axis.

    abstract::Osteoarthritis (OA) is a chronic disease that results in chronic arthralgia and functional disability of the affected joint. To date, there is no effective treatment available for this disease. Circular RNAs (circRNAs) are a type of intracellular stable RNA that can regulate the development and progression of OA. Howe...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2020.4772

    authors: Xiao J,Wang R,Zhou W,Cai X,Ye Z

    更新日期:2021-01-01 00:00:00

  • Identification of 12 novel loci that confer susceptibility to early-onset dyslipidemia.

    abstract::The circulating concentrations of triglycerides, high density lipoprotein (HDL)‑cholesterol, and low density lipoprotein (LDL)‑cholesterol have a substantial genetic component, and the heritability of early‑onset dyslipidemia might be expected to be higher compared with late‑onset forms. In the present study, exome‑wi...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3943

    authors: Yamada Y,Kato K,Oguri M,Horibe H,Fujimaki T,Yasukochi Y,Takeuchi I,Sakuma J

    更新日期:2019-01-01 00:00:00

  • Transcriptional targeting of virus-mediated gene transfer by the human hexokinase II promoter.

    abstract::The efficacy of the most commonly used form of suicide gene therapy, the HSV-TK/GCV method, utilizing herpes simplex virus thymidine kinase (HSV-TK) and antiviral drug ganciclovir (GCV) has been demonstrated in clinical trials. However, safer delivery of the therapeutic gene and more controlled regulation of the trans...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Määttä AM,Korja S,Venhoranta H,Hakkarainen T,Pirinen E,Heikkinen S,Pellinen R,Mäkinen K,Wahlfors J

    更新日期:2006-11-01 00:00:00

  • Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells.

    abstract::High-fidelity maintenance of genomic integrity in eukaryotes is ensured by cell cycle checkpoints and DNA repair. The checkpoint kinase, Chk2, has been implicated in both of these responses. In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation. The fully activated C...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Liang X,Reed E,Yu JJ

    更新日期:2006-05-01 00:00:00

  • Biochanin A attenuates LPS-induced pro-inflammatory responses and inhibits the activation of the MAPK pathway in BV2 microglial cells.

    abstract::Inflammation in the brain, characterized by the activation of microglia, is believed to participate in the pathogenesis of Parkinson's disease. Biochanin A, an O-methylated isoflavone, is a natural organic compound and is classified as a phytoestrogen. In this study, using murine BV2 microglial cells, we investigated ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2014.2020

    authors: Wu WY,Wu YY,Huang H,He C,Li WZ,Wang HL,Chen HQ,Yin YY

    更新日期:2015-02-01 00:00:00

  • MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway.

    abstract::The enhanced migratory ability of endometrial stromal cells (ESCs) is a key factor in the formation of functional endometrium‑like tissues outside the uterine cavity during endometriosis (EMS). Although accumulating evidence has suggested the importance of microRNAs (miRNAs) in the pathogenesis of EMS, the role of par...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2020.4749

    authors: Zhang D,Wang L,Guo HL,Zhang ZW,Wang C,Chian RC,Zhang ZF

    更新日期:2020-12-01 00:00:00

  • Allosteric regulation of the calcium-sensing receptor in obese individuals.

    abstract::We have previously reported that the calcium-sensing receptor (CaSR) plays an important role in modulating lipid metabolism under low calcium conditions. The aim of this study was to identify possible regulators of CaSR and the mechanisms of action of CaSR in obese individuals. Subcutaneous fat samples were obtained f...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2013.1408

    authors: He Y,Perry B,Bi M,Sun H,Zhao T,Li Y,Sun C

    更新日期:2013-08-01 00:00:00

  • Neuromedin-U stimulates enucleation-induced adrenocortical regeneration in the rat.

    abstract::Neuromedin-U (NMU) is a brain-gut peptide, which has been previously found to stimulate hypothalamic-pituitary-adrenal axis in the rat. Enucleation-induced adrenal regeneration in rats with contralateral adrenalectomy is a well-established model of adrenal growth, that not only depends on the compensatory ACTH hyperse...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Trejter M,Neri G,Rucinski M,Majchrzak M,Nussdorfer GG,Malendowicz LK

    更新日期:2008-06-01 00:00:00

  • Inhibitory effect of lactoperoxidase-generated hypothiocyanite upon black pigmented anaerobe growth.

    abstract::This study aimed to evaluate the in vitro effect of lactoperoxidase with or without its substrates (hydrogen peroxide, thiocyanate) on the growth of 4 different black pigmented anaerobe (BPA) strains associated with the development and progress of periodontal diseases: Porphyromonas gingivalis ATCC 33277, Prevotella i...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Fadel M,Courtois P

    更新日期:2001-07-01 00:00:00

  • Comparative integromics on FAT1, FAT2, FAT3 and FAT4.

    abstract::WNT5A, WNT5B, WNT11, FZD3, FZD6, VANGL1, VANGL2, DVL1, DVL2, DVL3, PRICKLE1, PRICKLE2, ANKRD6, NKD1, NKD2, DAAM1, DAAM2, CELSR1, CELSR2, CELSR3, ROR1 and ROR2 are planar cell polarity (PCP) signaling molecules implicated in the regulation of cellular polarity, convergent extension, and invasion. FAT1, FAT2, FAT3 and F...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Katoh Y,Katoh M

    更新日期:2006-09-01 00:00:00

  • Cytokine-induced neutrophil accumulation in the pathogenesis of acute reflux esophagitis in rats.

    abstract::Although recent reports indicate an increasing incidence of patients with reflux esophagitis, its pathomechanism remains unclear. Cytokines and neutrophils, the latter of which produce reactive oxygen species (ROS), have been implicated in the formation of gastrointestinal diseases. This study investigated the roles o...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Yamaguchi T,Yoshida N,Tomatsuri N,Takayama R,Katada K,Takagi T,Ichikawa H,Naito Y,Okanoue T,Yoshikawa T

    更新日期:2005-07-01 00:00:00

  • Chemoprotective effects of a recombinant protein from Pyropia yezoensis and synthetic peptide against acetaminophen-induced Chang liver cell death.

    abstract::In the present study, the chemoprotective effects of recombinant Pyropia yezoensis (P. yezoensis) protein 1 (PYP1) were examined in acetaminophen (APAP)-treated Chang liver cells. The analysis of P. yezoensis revealed the presence of both mature and immature variants of PYP1. PYP1s, designated as PYP1 (15 kDa), PYP1-A...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2015.2253

    authors: Choi YH,Kim EY,Mikami K,Nam TJ

    更新日期:2015-08-01 00:00:00

  • GATA binding protein 3 overexpression and suppression significantly contribute to the regulation of allergic skin inflammation.

    abstract::GATA binding protein 3 (GATA3) is a key molecule regulating the balance in the ratio of type 1 helper T (Th1) cells to type 2 helper T (Th2) cells, which is thought to be indicative of the pathogenesis of allergic diseases such as asthma and atopic dermatitis. The aim of this study was to investigate the role of GATA3...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2011.685

    authors: Bae CJ,Lee JW,Shim SB,Jee SW,Lee SH,Woo JM,Lee CK,Hwang DY

    更新日期:2011-08-01 00:00:00

  • Nardostachys chinensis induces the differentiation of human promyelocytic leukemic cells through the activation of the protein kinase C-dependent extracellular signal-regulated kinase signaling pathway.

    abstract::The underground parts of Nardostachys chinensis (N. chinensis), which belongs the genus Valerianaceae, have been used as sedative and analgesic agents in traditional Korean medicine for centuries. The mitogen-activated protein kinases (MAPKs) are serine/threonine kinases involved in the regulation of various cellular ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2013.1596

    authors: Ju SM,Kang JG,Pae HO,Lee GS,Kim WS,Lyu YS,Jeon BH

    更新日期:2014-03-01 00:00:00

  • COX-2 regulates E-cadherin expression through the NF-κB/Snail signaling pathway in gastric cancer.

    abstract::Cyclooxygenase-2 (COX-2) participates in cancer invasion and metastasis by decreasing the expression of E-cadherin. However, the molecular mechanisms through which COX-2 regulates E-cadherin expression and function have not yet been fully elucidated. The aim of this study was to investigate the possible molecular mech...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2013.1376

    authors: Chen Z,Liu M,Liu X,Huang S,Li L,Song B,Li H,Ren Q,Hu Z,Zhou Y,Qiao L

    更新日期:2013-07-01 00:00:00

  • Hepatic inflammatory cytokine production can be regulated by modulating sphingomyelinase and ceramide synthase 6.

    abstract::Chronic inflammation is associated with the pathogenesis of type 2 diabetes and diabetic complications, and palmitate has been nominated as a candidate for the molecular link between these disorders. Recently, a crucial role of ceramide in inflammation and metabolic diseases has been reported. Therefore, in this study...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2016.2835

    authors: Kim MH,Ahn HK,Lee EJ,Kim SJ,Kim YR,Park JW,Park WJ

    更新日期:2017-02-01 00:00:00

  • Microarray analysis of insulin-regulated gene expression in the liver: the use of transgenic mice co-expressing insulin-siRNA and human IDE as an animal model.

    abstract::To characterize the changes in global gene expression in the livers of H1/siRNAinsulin-CMV/hIDE transgenic (Tg) mice in response to the reduced bioavailability of insulin, total RNA extracted from the livers of 20-week-old Tg and non-Tg mice was converted to cDNA, labeled with biotin and hybridized to oligonucleotide ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Jee S,Hwang D,Seo S,Kim Y,Kim C,Kim B,Shim S,Lee S,Sin J,Bae C,Lee B,Jang M,Kim M,Yim S,Jang I,Cho J,Chae K

    更新日期:2007-12-01 00:00:00

  • Angiopoietin-2 promotes extracellular matrix degradation in human degenerative nucleus pulposus cells.

    abstract::In contrast to healthy intervertebral discs (IVDs), degenerate IVDs become vascularized. Here, we determined the role of an angiogenesis promoter, angiopoietin (Ang)-2, in the pathology of IVD degeneration (IDD). We evaluated degree of IDD using the Pfirrmann grading system. We used quantitative real-time polymerase c...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3576

    authors: Wang K,Kang L,Liu W,Song Y,Wu X,Zhang Y,Hua W,Zhao K,Li S,Tu J,Luo R,Yang C

    更新日期:2018-06-01 00:00:00

  • [Corrigendum] Correlation between the expression of IL‑18 and deep venous thrombosis.

    abstract::In the above paper, the authors realize that an error inadvertently appeared in the funding section on p. 895. Where "This study was supported by the National Natural Science Foundation of China Science Fund Project (grant no. 30960389 and 8176010097)" was written, the application number 8176010097 was featured incorr...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3843

    authors: Li G,Zhou R,Zhao X,Liu R,Ye C

    更新日期:2018-08-27 00:00:00