scholarly journals Piceatannol-mediated alteration of amyloidogenesis in SH-SY5Y neuroblastoma cells treated with amyloid-beta

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Yun Jung Yang ◽  
Hee Yun Cha ◽  
Soo Jin Yang
Keyword(s):  
Amyloid Precursor Protein ◽  
Cell Viability ◽  
Amyloid Beta ◽  
High Glucose ◽  
Neuroblastoma Cells ◽  
Conditioned Media ◽  
Precursor Protein ◽  
High Concentration ◽  
High Glucose Condition ◽  
Glucose Condition

AbstractHigh glucose condition impairs neuronal integrity and function by regulating amyloidogenesis and neuroinflammation. Here, we pursue to investigate whether high glucose condition leads impairments in neuronal integrity/function by inducing amyloidogenesis and neuroinflammation, and whether piceatannol (PIC) restores high glucose condition-induced deteriorations in neuronal cells. High glucose condition was induced by maintaining SH-SY5Y neuroblastoma cells in 25 mM glucose. In addition, amyloid-beta was applied to make the cells having amyloidogenesis-mediated deleterious alterations. Cells were maintained in low glucose (2.5 mM glucose) or high glucose (25 mM glucose) condition. And, two doses (10 and 20 μM) of PIC and/or 10 μM of amyloid-beta were treated in a subset of cells for 24 h. There were no significant differences in cell morphology and cell viability among groups. PIC treatment did not show cell toxicity based on cell viability assessed by PrestoBlue assay. High concentration of glucose and amyloid-beta treatments increased amyloid-beta concentrations in cell lysates and conditioned media, which were reduced by PIC. 10 μM PIC treatment for 24 h decreased amyloid precursor protein (APP), beta-site amyloid precursor protein cleaving enzyme-1, presenilin (PS) 1 and tau. Among analyzed inflammatory markers, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were reduced in conditioned media by 10 μM PIC administration for 24 h. These data indicate that high glucose condition may result in excessive levels of amyloidogenesis and neuroinflammation as well as subsequent changes in neuronal integrity/function, and that PIC treatment may ameliorate the deleterious consequences from high glucose and amyloid-beta treatments.

scholarly journals Combination of ferric ammonium citrate with cytokines involved in apoptosis and insulin secretion of human pancreatic beta cells related to diabetes in thalassemia

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9298
Author(s):  
Patchara Rattanaporn ◽  
Sissades Tongsima ◽  
Thomas Mandrup-Poulsen ◽  
Saovaros Svasti ◽  
Dalina Tanyong
Keyword(s):  
Insulin Secretion ◽  
Cell Viability ◽  
High Glucose ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
High Glucose Condition ◽  
Genes Expression ◽  
Tnf Α ◽  
Ferric Ammonium ◽  
Glucose Condition

Background Diabetes mellitus (DM) is a common complication found in β-thalassemia patients. The mechanism of DM in β-thalassemia patients is still unclear, but it could be from an iron overload and increase of some cytokines, such as interleukin1-β (IL-1β) and tumor necrosis factor-α (TNF-α). The objective of this study was to study the effect of interaction between ferric ammonium citrate (FAC) and cytokines, IL-1β and TNF-α, on 1.1B4 human pancreatic β-cell line. Methods The effect of the combination of FAC and cytokines on cell viability was studied by MTT assay. Insulin secretion was assessed by the enzyme-linked immunosorbent assay (ELISA). The reactive oxygen species (ROS) and cell apoptosis in normal and high glucose condition were determined by flow cytometer. In addition, gene expression of apoptosis, antioxidant; glutathione peroxidase 1 (GPX1) and superoxide dismutase 2 (SOD2), and insulin secretory function were studied by real-time polymerase chain reaction (Real-time PCR). Results The findings revealed that FAC exposure resulted in the decrease of cell viability and insulin-release, and the induction of ROS and apoptosis in pancreatic cells. Interestingly, a combination of FAC and cytokines had an additive effect on SOD2 antioxidants’ genes expression and endoplasmic reticulum (ER) stress. In addition, it reduced the insulin secretion genes expression; insulin (INS), glucose kinase (GCK), protein convertase 1 (PSCK1), and protein convertase 2 (PSCK2). Moreover, the highest ROS and the lowest insulin secretion were found in FAC combined with IL-1β and TNF-α in the high-glucose condition of human pancreatic beta cell, which could be involved in the mechanism of DM development in β-thalassemia patients.

G-lymphatic, vascular and immune pathways for Aβ clearance cascade and therapeutic targets for Alzheimer’s disease

2020 ◽  
Vol 23 ◽  
Author(s):  
Saurav Chakraborty ◽  
Jyothsna ThimmaReddygari ◽  
Divakar Selvaraj
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Complement System ◽  
Therapeutic Targets ◽  
Neuronal Cell ◽  
Precursor Protein ◽  
Amyloid Beta Peptide ◽  
Beta Peptide ◽  
Immune Pathways

The Alzheimer disease is a age related neurodegenerative disease. The factors causing alzheimer disease are numerous. Research on humans and rodent models predicted various causative factors involved in Alzheimer disease progression. Among them, neuroinflammation, oxidative stress and apoptosis play a major role because of accumulation of extracellular amyloid beta peptides. Here, the clearance of amyloid beta peptide plays a major role because of the imbalance in the production and clearance of the amyloid beta peptide. Additionally, neuroinflammation by microglia, astrocytes, cytokines, chemokines and the complement system also have a major role in Alzheimer disease. The physiological clearance pathways involved in amyloid beta peptide are glymphatic, vascular and immune pathways. Amyloid precursor protein, low density lipoprotein receptor-related protein 1, receptor for advanced glycation end product, apolipoprotein E, clusterin, aquaporin 4, auto-antibodies, complement system, cytokines and microglia are involved in amyloid beta peptide clearance pathways across the blood brain barrier. The plaque formation in the brain by alternative splicing of amyloid precursor protein and production of misfolded protein results in amyloid beta agglomeration. This insoluble amyloid beta leads to neurodegenerative cascade and neuronal cell death occurs. Studies had shown disturbed sleep may be a risk factor for dementia and cognitive decline. In this review, the therapeutic targets for alzheimer disease via focussing on pathways for amyloid beta clearance are discussed.

scholarly journals Remodeling Alzheimer-amyloidosis models by seeding

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Brittany S. Ulm ◽  
David R. Borchelt ◽  
Brenda D. Moore
Keyword(s):  
Amyloid Precursor Protein ◽  
Neurodegenerative Diseases ◽  
Amyloid Beta ◽  
Precursor Protein ◽  
Time Interval ◽  
Murine Models ◽  
Brain Pathology ◽  
Amyloid Deposits ◽  
Transgenic Murine Models ◽  
Mutant Genes

AbstractAlzheimer’s disease (AD) is among the most prevalent neurodegenerative diseases, with brain pathology defined by extracellular amyloid beta deposits and intracellular tau aggregates. To aid in research efforts to improve understanding of this disease, transgenic murine models have been developed that replicate aspects of AD pathology. Familial AD is associated with mutations in the amyloid precursor protein and in the presenilins (associated with amyloidosis); transgenic amyloid models feature one or more of these mutant genes. Recent advances in seeding methods provide a means to alter the morphology of resultant amyloid deposits and the age that pathology develops. In this review, we discuss the variety of factors that influence the seeding of amyloid beta pathology, including the source of seed, the time interval after seeding, the nature of the transgenic host, and the preparation of the seeding inoculum.

scholarly journals Presenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid beta -protein generation

2000 ◽  
Vol 97 (16) ◽  
pp. 9299-9304 ◽  
Author(s):  
W. Xia ◽  
W. J. Ray ◽  
B. L. Ostaszewski ◽  
T. Rahmati ◽  
W. T. Kimberly ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Precursor Protein ◽  
Amyloid Beta Protein
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