Abstract:
:Increased plasma homocysteinemia is considered a risk factor of dementia, including Alzheimer's disease (AD) and vascular dementia. However, the reason elevated plasma homocysteinemia increases the risk of dementia remains unknown. A pathological hallmark of AD is neurofibrillary tangles (NFTs) that consist of pathologically phosphorylated tau proteins. The effect of homocysteine (Hcy) on tau aggregation was explored using human neuroblastoma M1C cells that constitutively express human wild-type tau (4R0N) under the control of a tetracycline off system, primary mouse cultured neurons, and by inducing hyperhomocysteinemia in a mouse model of tauopathy (HHCy mice). A wide range of Hcy concentrations (10-1000 µM) increased total tau and phosphorylated tau protein levels. Hcy activated glycogen synthase kinase 3, and cyclin dependent kinase 5, major tau phosphokinases, and inactivated protein phosphatase 2A, a main tau phosphatase. Hcy exhibited cytotoxic effects associated with enhanced activation of caspase. Truncation of tau in the C-terminus, the cleavage site of caspase 3 (i.e., D421, detected by the TauC3 antibody) was also increased. Total tau, phosphorylated tau, as well as C-terminal cleaved tau were increased in the sarkosyl insoluble tau fraction. Hcy also increased the level of tau oligomers, as indicated by the tau oligomer complex 1 (TOC1) antibody that specifically identifies oligomeric tau species, in the tris insoluble, sarkosyl soluble fraction. The levels of TOC1-positive oligomeric tau were increased in brain lysates from HHCy mice, and treating HHCy mice with S-adenosylmethionine, an intermediate of Hcy, reduced the levels of oligomeric tau to control levels. These observations suggest that Hcy increases the levels of phosphorylated tau as well as truncated tau species via caspase 3 activation, and enhanced tau oligomerization and aggregation.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Shirafuji N,Hamano T,Yen SH,Kanaan NM,Yoshida H,Hayashi K,Ikawa M,Yamamura O,Kuriyama M,Nakamoto Ydoi
10.3390/ijms19030891subject
Has Abstractpub_date
2018-03-17 00:00:00issue
3issn
1422-0067pii
ijms19030891journal_volume
19pub_type
杂志文章abstract::The phase-transition temperatures of an elastin-like polypeptide (ELP) with the (GVGVP)40 sequence and solvent dipolarity/polarizability, hydrogen-bond donor acidity, and hydrogen-bond acceptor basicity in its aqueous solutions were quantified in the absence and presence of different salts (Na2SO4, NaCl, NaClO4, and N...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms160613528
更新日期:2015-06-12 00:00:00
abstract::Given their extremely small size and light weight, carbon nanotubes (CNTs) can be readily inhaled by human lungs resulting in increased rates of pulmonary disorders, particularly fibrosis. Although the fibrogenic potential of CNTs is well established, there is a lack of consensus regarding the contribution of physicoc...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms15057444
更新日期:2014-04-29 00:00:00
abstract::In this work, we developed quantitative structure-activity relationships (QSAR) models for prediction of oxygen radical absorbance capacity (ORAC) of flavonoids. Both linear (partial least squares-PLS) and non-linear models (artificial neural networks-ANNs) were built using parameters of two well-established antioxida...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20092328
更新日期:2019-05-10 00:00:00
abstract::Cynoglossus semilaevis is an important economic fish species and has long been cultivated in China. Since the completion of its genome and transcriptome sequencing, genes relating to C. semilaevis development have been extensively studied. R-spondin 3 (Rspo3) is a member of the R-spondin family. It plays an important ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19071915
更新日期:2018-06-29 00:00:00
abstract::The gadolinium-based nanoagent named AGuIX® is a unique radiosensitizer and contrast agent which improves the performance of radiotherapy and medical imaging. Currently tested in clinical trials, AGuIX® is administrated to patients via intravenous injection. The presence of nanoparticles in the blood stream may induce...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21134673
更新日期:2020-06-30 00:00:00
abstract::This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs s...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms14024174
更新日期:2013-02-19 00:00:00
abstract::Regenerative medicine has rapidly evolved, due to progress in cell and molecular biology allowing the isolation, characterization, expansion, and engineering of cells as therapeutic tools. Despite past limited success in the clinical translation of several promising preclinical results, this novel field is now enterin...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms18051021
更新日期:2017-05-09 00:00:00
abstract::The Gram-negative Campylobacter jejuni is a major cause of foodborne gastroenteritis in humans worldwide. The cytotoxic effects of Campylobacter have been mainly ascribed to the actions of the cytolethal distending toxin (CDT): it is mandatory to put in evidence risk factors for sequela development, such as reactive a...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21062207
更新日期:2020-03-23 00:00:00
abstract::microRNA-143(miR-143) is a well-known tumor suppressive microRNA that exhibits anti-tumoral function by targeting KRAS signaling pathways in various malignancies. We hypothesized that miR-143 suppresses breast cancer progression by targeting KRAS and its effector molecules. We further hypothesized that high expression...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21093213
更新日期:2020-05-01 00:00:00
abstract::It is widely accepted that chronic inflammation initiates and promotes carcinogenesis and tumor progression in various cell types. However, this paradigm has not been comprehensively investigated in melanoma. To investigate the effects of chronic inflammation on the progression of melanoma, we established a murine inf...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20010169
更新日期:2019-01-04 00:00:00
abstract::Matrix metalloproteinases (MMPs) are enzymes involved in periodontal tissue destruction. Hemagglutinin B (HagB) from the periodontal pathogen Porphyromonas gingivalis induces an elevated MMP response in dendritic cells, but responses from cultures of single-cell types do not reflect the local tissue environment. The o...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19123923
更新日期:2018-12-07 00:00:00
abstract::Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms140510242
更新日期:2013-05-16 00:00:00
abstract::The outermost barrier layer of the skin is the stratum corneum (SC), which consists of corneocytes embedded in a lipid matrix. Biosynthesis of barrier lipids occurs de novo in the epidermis or is performed with externally derived lipids. Hence, in vitro developed human skin equivalents (HSEs) are developed with cultur...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20236069
更新日期:2019-12-02 00:00:00
abstract::Exosomes, the smallest group of extracellular vesicles, carry proteins, miRNA, mRNA, DNA, and lipids, which they efficiently deliver to recipient cells, generating a communication network. Exosomes strongly contribute to the immune suppressive tumor microenvironment of head and neck squamous cell carcinomas (HNSCC). I...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21114072
更新日期:2020-06-06 00:00:00
abstract::The purpose of the study was to investigate the antioxidant characteristics of Anisomeles indica methanol extract and the inhibitory effect of ovatodiolide on melanogenesis. In the study, the antioxidant capacities of A. indica methanol extract such as DPPH assay, ABTS radical scavenging assay, reducing capacity and m...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms13056220
更新日期:2012-01-01 00:00:00
abstract::Many nutrients are absorbed via Na+ cotransport systems, and therefore it is predicted that nutrient absorption mechanisms require a large amount of luminal Na+. It is thought that Na+ diffuses back into the lumen via paracellular pathways to support Na+ cotransport absorption. However, direct experimental evidence in...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21020376
更新日期:2020-01-07 00:00:00
abstract::The conserved serine/threonine kinase mTOR (the mammalian target of rapamycin), a downstream effector of the PI3K/AKT pathway, forms two distinct multiprotein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to rapamycin, activates S6K1 and 4EBP1, which are involved in mRNA translation. It is activated by diverse sti...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms13021886
更新日期:2012-01-01 00:00:00
abstract::Buckwheat is an important functional food material with high nutritional value. However, it is still a difficult task for the taxonomy studies of wild buckwheat that are only based on morphology. In order to demonstrate the most efficient DNA barcode in the phylogenetic research of buckwheat, promote the investigation...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20143455
更新日期:2019-07-14 00:00:00
abstract::Larix olgensis Henry is an important coniferous species found in plantation forests in northeastern China, but it is vulnerable to pathogens. Nitric oxide (NO) is an important molecule involved in plant resistance to pathogens. To study the regulatory role of NO at the transcriptional level, we characterized the trans...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms161226117
更新日期:2015-12-02 00:00:00
abstract::Homologous recombination (HR) is often used to achieve targeted gene integration because of its higher precision and operability compared with microhomology-mediated end-joining (MMEJ) or non-homologous end-joining (NHEJ). It appears to be inefficient for gene integration in animal cells and embryos due to occurring o...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21165821
更新日期:2020-08-13 00:00:00
abstract::Extracellular vesicles (EVs) are a heterogeneous group of particles, between 15 nanometers and 10 microns in diameter, released by almost all cell types in physiological and pathological conditions, including tumors. EVs have recently emerged as particularly interesting informative vehicles, so that they could be cons...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms18061183
更新日期:2017-06-02 00:00:00
abstract::Chronic immune response to bone implant may lead to delayed healing and its failure. Thus, newly developed biomaterials should be characterized by high biocompatibility. Moreover, it is well known that macrophages play a crucial role in the controlling of biomaterial-induced inflammatory response. Immune cells synthes...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms22031109
更新日期:2021-01-23 00:00:00
abstract::Mitochondria are complex organelles that play critical roles in diverse aspects of cellular function. Heart disease and a number of other pathologies are associated with perturbations in the molecular machinery of the mitochondria. Therefore, comprehensive, unbiased examination of the mitochondrial proteome represents...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms15069285
更新日期:2014-05-26 00:00:00
abstract::Cyclosporin A (CsA), a calcineurin inhibitor, remain the cornerstone of immunosuppressive regimens, regardless of nephrotoxicity, which depends on the duration of drug exposure. The mechanisms and biomarkers underlying the transition from CsA-induced renal dysfunction to nephrotoxicity deserve better elucidation, and ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms15058979
更新日期:2014-05-20 00:00:00
abstract::Frataxin is a highly conserved protein whose deficiency results in the neurodegenerative disease Friederich's ataxia. Frataxin's actual physiological function has been debated for a long time without reaching a general agreement; however, it is commonly accepted that the protein is involved in the biosynthetic iron-su...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21249619
更新日期:2020-12-17 00:00:00
abstract::Two amantadine (ATD)-gardenamide A (GA) ligands have been designed and synthesized. The bonding of ATD with GA through a methylene carbonyl brigde (L1) enhances the neuroprotective effect against corticosterone (CORT)-induced impairments in PC12 cells; while the bonding through a succinyl brigde (L2) does not. L1 redu...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms160922795
更新日期:2015-09-21 00:00:00
abstract::Gastric cancer (GC) is a deadly disease with poor prognosis that is characterized by heterogeneity. New classifications based on histologic features, genotypes, and molecular phenotypes, for example, the Cancer Genome Atlas subtypes and those by the Asian Cancer Research Group, help understand the carcinogenic differe...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21249400
更新日期:2020-12-10 00:00:00
abstract::Dietary fats and sugars were identified as risk factors for overweight and neurodegeneration, especially in middle-age, an earlier stage of the aging process. Therefore, our aim was to study the metabolic response of both white adipose tissue and brain in middle aged rats fed a typical Western diet (high in saturated ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21030786
更新日期:2020-01-25 00:00:00
abstract::Fumarylacetoacetate hydrolase (FAH) is the last enzyme in the degradation pathway of the amino acids tyrosine and phenylalanine in mammals that catalyzes the hydrolysis of 4-fumarylacetoacetate into acetoacetate and fumarate. Mutations of the FAH gene are associated with hereditary tyrosinemia type I (HT1), resulting ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21228719
更新日期:2020-11-18 00:00:00
abstract::Anoectochilus roxburghii is a traditional Chinese herb with high medicinal value, with main bioactive constituents which are flavonoids. It commonly associates with mycorrhizal fungi for its growth and development. Moreover, mycorrhizal fungi can induce changes in the internal metabolism of host plants. However, its r...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21020564
更新日期:2020-01-15 00:00:00