Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Int J Mol Sci ; 25(10)2024 May 10.
Article in English | MEDLINE | ID: mdl-38791263

ABSTRACT

Stroke and Alzheimer's disease (AD) are prevalent age-related diseases; however, the relationship between these two diseases remains unclear. In this study, we aimed to investigate the ability of melatonin, a hormone produced by the pineal gland, to alleviate the effects of ischemic stroke leading to AD by observing the pathogenesis of AD hallmarks. We utilized SH-SY5Y cells under the conditions of oxygen-glucose deprivation (OGD) and oxygen-glucose deprivation and reoxygenation (OGD/R) to establish ischemic stroke conditions. We detected that hypoxia-inducible factor-1α (HIF-1α), an indicator of ischemic stroke, was highly upregulated at both the protein and mRNA levels under OGD conditions. Melatonin significantly downregulated both HIF-1α mRNA and protein expression under OGD/R conditions. We detected the upregulation of ß-site APP-cleaving enzyme 1 (BACE1) mRNA and protein expression under both OGD and OGD/R conditions, while 10 µM of melatonin attenuated these effects and inhibited beta amyloid (Aß) production. Furthermore, we demonstrated that OGD/R conditions were able to activate the BACE1 promoter, while melatonin inhibited this effect. The present results indicate that melatonin has a significant impact on preventing the aberrant development of ischemic stroke, which can lead to the development of AD, providing new insight into the prevention of AD and potential stroke treatments.


Subject(s)
Alzheimer Disease , Amyloid Precursor Protein Secretases , Melatonin , Neuroblastoma , Melatonin/pharmacology , Humans , Alzheimer Disease/metabolism , Alzheimer Disease/etiology , Alzheimer Disease/pathology , Neuroblastoma/metabolism , Neuroblastoma/pathology , Cell Line, Tumor , Amyloid Precursor Protein Secretases/metabolism , Aspartic Acid Endopeptidases/metabolism , Aspartic Acid Endopeptidases/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Glucose/metabolism , Amyloid beta-Peptides/metabolism , Oxygen/metabolism , Cell Hypoxia/drug effects , Hypoxia/metabolism
2.
Fish Shellfish Immunol ; 123: 528-536, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35337980

ABSTRACT

Intelectins are immune lectins expressed in chordates, including several fish species, in which intelectins are known to be upregulated upon infection. However, the basic biochemical properties and bacteria binding specificities of several fish intelectins are not well studied. We focus our investigation on zebrafish intelectin-2 (DrIntL-2) that is predominantly expressed in the gastrointestinal tract. The disulfide-linked oligomeric state and the cysteine responsible for intermolecular disulfide bonds are identified. DrIntL-2 is a globular particle of around 30 nm. In addition to the typical exocyclic 1,2-diol ligands, DrIntL-2 binds ß-1,3-glucan and recognizes Salmonella typhimurium and Pseudomonas aeruginosa. This investigation not only shed light on the fish innate immunity that will be essential for the aquaculture industry, but will also provide a foundation for further application of DrIntL-2 in bacteria detection and identification.


Subject(s)
Cytokines , Zebrafish , Amino Acid Sequence , Animals , Cytokines/metabolism , Disulfides , Immunity, Innate , Ligands
3.
Sci Rep ; 11(1): 2934, 2021 02 03.
Article in English | MEDLINE | ID: mdl-33536457

ABSTRACT

Fibrinogen-related lectins are carbohydrate-binding proteins of the innate immune system that recognize glycan structures on microbial surfaces. These innate immune lectins are crucial for invertebrates as they do not rely on adaptive immunity for pathogen clearance. Here, we characterize a recombinant fibrinogen-related lectin PmFREP from the black tiger shrimp Penaeus monodon expressed in the Trichoplusia ni insect cell. Electron microscopy and cross-linking experiments revealed that PmFREP is a disulfide-linked dimer of pentamers distinct from other fibrinogen-related lectins. The full-length protein binds N-acetyl sugars in a Ca2+ ion-independent manner. PmFREP recognized and agglutinated Pseudomonas aeruginosa. Weak binding was detected with other bacteria, including Vibrio parahaemolyticus, but no agglutination activity was observed. The biologically active PmFREP will not only be a crucial tool to elucidate the innate immune signaling in P. monodon and other economically important species, but will also aid in detection and prevention of shrimp bacterial infectious diseases.


Subject(s)
Arthropod Proteins/immunology , Fibrinogen/immunology , Penaeidae/immunology , Recombinant Proteins/immunology , Amino Acid Sequence , Animals , Arthropod Proteins/chemistry , Arthropod Proteins/genetics , Arthropod Proteins/ultrastructure , Cell Line , Fibrinogen/chemistry , Fibrinogen/genetics , Fibrinogen/ultrastructure , Immunity, Innate , Insecta , Microscopy, Electron , Penaeidae/genetics , Penaeidae/microbiology , Phylogeny , Protein Conformation, alpha-Helical , Pseudomonas aeruginosa/immunology , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/ultrastructure , Vibrio parahaemolyticus/immunology
4.
J Cell Commun Signal ; 13(2): 245-254, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30264361

ABSTRACT

Notch signaling has been reported to correlate with tumor progression and metastasis in several types of cancer. In cholangiocarcinoma (CCA), it has recently been shown that NOTCH1 is overexpressed in both nucleus and cytoplasm of CCA cells; however, the complete understanding of Notch signaling in CCA is still lacking. Here, we aimed to understand the functions of NOTCH1 in CCA cells and the molecular mechanisms that underlie those functions. We used retroviral vectors to overexpress active forms of NOTCH1, the NOTCH1 intracellular domain (N1ICD) and N1ICD that lacks the RBP-J-associated module (RAM), in human CCA cell lines RMCCA-1 and HuCCA-1. Our results showed that activation of Notch signaling by both N1ICD variants enhanced CCA cell proliferation and survival via upregulation of pro-survival protein Mcl-1 and Bcl-xL. Moreover, our LC-MS/MS proteomic studies demonstrated that NOTCH1 may cooperate with 14-3-3 theta to promote CCA cell survival. Knockdown of 14-3-3 theta in RMCCA-1 cells overexpressing N1ICD, diminished pro-survival effects of N1ICD under gemcitabine treatment. In conclusion, these data demonstrated that NOTCH1 plays a role in CCA cell proliferation and survival via the regulation of 14-3-3 theta in a RAM-independent fashion.

SELECTION OF CITATIONS
SEARCH DETAIL
...