Редактирование: FADD

FAS-associated death domain protein (FAS-associating death domain-containing protein) (Growth-inhibiting gene 3 protein) (Mediator of receptor induced toxicity) (Protein FADD) [MORT1] [GIG3]

==Publications==

{{medline-entry
|title=Voluntary exercise training attenuated the middle-aged maturity-induced cardiac apoptosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32781061
|abstract=Voluntary exercise training has cardioprotective effects in humans, but the underlying mechanism is unknown. This research was done to estimate the effect of voluntary exercise training to attenuate middle-aged maturity-induced cardiac apoptosis. The study was designed to divide 64 male mice randomly into four groups, consisting of a 9-month sedentary pre-middle-aged group (9M), 15-month sedentary middle-aged group (15M), and two exercise groups using a voluntary wheel running respectively (9M EX, 15M EX). After 3 months, the condition of cardiac apoptosis in different groups was measured by HE dying, TUNEL and DAPI staining, and Western Blot analysis. TUNEL-positive cells were increased in 15M group compared with 9M group, while decreased in 9M EX and 15M EX groups compared with their control groups respectively. Protein levels of AIF, Endo G, [[TNF]]-α, [[TNF]]R1, [[TRAF2]], [[TRADD]], Fas, FasL, [[FADD]], activated caspase 8, 3, 9, Bax/Bcl2, Bak/BclxL, and tBid were decreased in 9M EX and 15M EX groups compared with their control groups respectively. The protein levels of pBad/Bad, 14-3-3, [[IGF1]], IGFR1, pPI3K/PI3K, and pAKT/AKT were more activated in the 9M EX and 15M EX groups than those in their control groups respectively. Significant differences were found between 9M group and 15M group for the protein levels of [[TRAF2]], [[FADD]], Bax/Bcl2, tBid and pAKT/AKT. Voluntary exercise training as an important lifestyle modification may prevent cardiac widely dispersed apoptosis and enhance cardiac survival at middle-aged maturity.
|mesh-terms=* Aging
* Animals
* Apoptosis
* Heart
* In Situ Nick-End Labeling
* Male
* Mice
* Mice, Inbred C57BL
* Mitochondria, Heart
* Muscle, Skeletal
* Physical Conditioning, Animal
* Running
* Sedentary Behavior
|keywords=* Caspase-independent
* Cell death
* Fas dependent
* IGF-related
* Mitochondrial
|full-text-url=https://sci-hub.do/10.1016/j.lfs.2020.118187
}}
{{medline-entry
|title=[[[FAS]]- and [[TNF]]-dependent ways participation in apoptosis mechanisms in hypotalumus in physiological and pathological aging.]
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32362081
|abstract=The cell resistance to apoptosis can be related to the activity of cytokine-dependent signaling. So, the aim of the work is to investigate the mechanisms of cytokine-dependent [[FAS]]/[[TNF]]-mediated regulation of apoptosis of neurosecretory cells in the physiological and pathological (overexpression of the oncogene HER-2/Neu) aging. HER2/Neu transgenic accelerated aged mice of different ages and wild type FVB/N were examined. The apoptosis level of neurons in hypothalamic sections (supraoptic and paraventricular nuclei) (TUNEL) and expression of caspase-8, CD178 ([[FAS]]L), [[FAS]], [[FADD]], [[TRADD]] (Western blotting) was determined. Participation of the proinflammatory component in the aging process is shown. [[FAS]], adapter proteins associated with the death domain ([[FADD]] and [[TRADD]]), caspase-8 expression is activated in hypothalamus in FVB/N mice (wild type) during aging, and it correlates with an increase in the apoptosis level. HER-2/Neu expression leads to the extrinsic apoptotic pathway suppression. In this case, the reception of an apoptotic signal ([[FAS]]-receptor expression) and its further transmission (expression of [[FADD]] and [[TRADD]]) is suppressed. However, in young transgenic mice, increased expression of [[TRADD]] can activate one of the survival ways - NF-κB, ERK or PI3K-AKT cascade. Thus, the HER-2/Neu tyrosine kinase receptor plays a role in the mechanism of cell resistance to age-dependent apoptosis, and the [[FAS]]/[[TNF]]-signaling pathway is one of the targets of HER-2/Neu.
|mesh-terms=* Aging
* Animals
* Apoptosis
* Female
* Hypothalamus
* Mice
* Mice, Transgenic
* Signal Transduction
* Tumor Necrosis Factor-alpha
* fas Receptor
|keywords=* FAS-, TNF-dependent pathways
* aging
* apoptosis
* hypothalamus
* neurons

}}
{{medline-entry
|title=Anti-Apoptotic Effects of Diosgenin in D-Galactose-Induced Aging Brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32138534
|abstract=The purpose of this study was to evaluate the effects of diosgenin on the D-galactose-induced cerebral cortical widely dispersed apoptosis. Male 12-week-old Wistar rats were divided into four groups: Control (1 mg/kg/day of saline, i.p.), DD0 (150 mg/kg/day of D-galactose, i.p.), DD10, and DD50 (D-galactose  or 50 mg/kg/day of diosgenin orally). After eight weeks, histopathological analysis, positive TUNEL and Western blotting assays were performed on the excised cerebral cortex from all four groups. The TUNEL-positive apoptotic cells, the components of Fas pathway (Fas, [[FADD]], active caspase-8 and active caspase-3), and mitochondria pathway (t-Bid, Bax, cytochrome  , active caspase-9 and active caspase-3) were increased in the DD0 group compared with the control group, whereas they were decreased in the DD50 group. The components of survival pathway (p-Bad, Bcl-2, Bcl-xL, IGF-1, p-PI3K and p-AKT) were increased in the DD50 group compared to the control group, whereas the levels of Bcl-xL, p-PI3K, and p-AKT were also compensatorily increased in the DD0 group compared to the control group. Taken together, diosgenin suppressed D-galactose-induced neuronal Fas-dependent and mitochondria-dependent apoptotic pathways and enhanced the Bcl-2 family associated pro-survival and IGF-1-PI3K-AKT survival pathways, which might provide neuroprotective effects of diosgenin for prevention of the D-galactose-induced aging brain.
|mesh-terms=* Aging
* Animals
* Apoptosis
* Brain
* Caspase 3
* Caspase 8
* Diosgenin
* Fas-Associated Death Domain Protein
* Insulin-Like Growth Factor I
* Male
* Mitochondria
* Neuroprotective Agents
* Phosphatidylinositol 3-Kinases
* Proto-Oncogene Proteins c-akt
* Proto-Oncogene Proteins c-bcl-2
* Rats, Wistar
* Signal Transduction
* fas Receptor
|keywords=* Aging
* Apoptosis
* Brain
* D-galactose
* Diosgenin
* Survival
|full-text-url=https://sci-hub.do/10.1142/S0192415X20500202
}}
{{medline-entry
|title=Improved age-related deficits in cognitive performance and affective-like behavior following acute, but not repeated, 8-OH-DPAT treatments in rats: regulation of hippocampal [[FADD]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30138765
|abstract=The aims of this study were (1) to behaviorally phenotype rats at different ages for both cognitive performance and affect, (2) to evaluate the possible beneficial effects of 8-OH-DPAT (a 5-HT  receptor agonist) treatments on improving age-related behavioral deficits, and (3) to uncover putative key brain targets (e.g., Fas-associated protein with death domain [[[FADD]]] and related partners) that might contribute to the observed age-related behavioral changes. The principal results showed that acute, but not repeated, 8-OH-DPAT treatments improved age-related deficits in cognitive performance and affect while induced hypothermia. Moreover, multifunctional [[FADD]] protein decreased with age specifically in the hippocampus (as compared to the prefrontal cortex) and was further decreased following acute 8-OH-DPAT. The major conclusions indicate a parallelism between the beneficial effects observed following acute 8-OH-DPAT on improving the negative consequences of aging on cognition and affect, together with the acute induction of hypothermia and hippocampal [[FADD]] regulation. Because these effects were not observed following repeated treatment (i.e., observed tolerance to acute hypothermia), the results suggest 5-HT  receptors desensitization and/or the activation of compensatory adaptive mechanisms.
|mesh-terms=* 8-Hydroxy-2-(di-n-propylamino)tetralin
* Affect
* Animals
* Behavior, Animal
* Fas-Associated Death Domain Protein
* Hippocampus
* Hypothermia
* Male
* Maze Learning
* Rats, Sprague-Dawley
* Serotonin Receptor Agonists
|keywords=* 8-OH-DPAT
* Aging
* Cognition
* FADD
* Hippocampus
* Hypothermia
|full-text-url=https://sci-hub.do/10.1016/j.neurobiolaging.2018.07.014
}}
{{medline-entry
|title=Decreased cortical [[FADD]] protein is associated with clinical dementia and cognitive decline in an elderly community sample.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28320441
|abstract=[[FADD]] (Fas-associated death domain) adaptor is a crucial protein involved in the induction of cell death but also mediates non-apoptotic actions via a phosphorylated form (p-Ser194-[[FADD]]). This study investigated the possible association of [[FADD]] forms with age-related neuropathologies, cognitive function, and the odds of dementia in an elderly community sample. [[FADD]] forms were quantified by western blot analysis in dorsolateral prefrontal cortex (DLPFC) samples from a large cohort of participants in a community-based aging study (Memory and Aging Project, MAP), experiencing no-(NCI, n = 51) or mild-(MCI, n = 42) cognitive impairment, or dementia (n = 57). Cortical [[FADD]] was lower in subjects with dementia and lower [[FADD]] was associated with a greater load of amyloid-β pathology, fewer presynaptic terminal markers, poorer cognitive function and increased odds of dementia. Together with the observations of [[FADD]] redistribution into tangles and dystrophic neurites within plaques in Alzheimer's disease brains, and its reduction in APP23 mouse cortex, the results suggest this multifunctional protein might participate in the mechanisms linking amyloid and tau pathologies during the course of the illness. The present data suggests [[FADD]] as a putative biomarker for pathological processes associated with the course of clinical dementia.
|mesh-terms=* Aged, 80 and over
* Animals
* Biomarkers
* Blotting, Western
* Cognitive Dysfunction
* Fas-Associated Death Domain Protein
* Female
* Fluorescent Antibody Technique
* Humans
* Male
* Mice
* Mice, Transgenic
* Prefrontal Cortex
|keywords=* Aging
* Alzheimer’s disease
* Apoptosis
* Neuroplasticity
* Neurotoxicity
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360099
}}
{{medline-entry
|title=Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26068050
|abstract=While hippocampus is a brain region particularly susceptible to the effects of MDMA, the cellular and molecular changes induced by MDMA are still to be fully elucidated, being the dosage regimen, the species and the developmental stage under study great variables. This study compared the effects of one and four days of MDMA administration following a binge paradigm (3×5 mg/kg, i.p., every 2 h) on inducing hippocampal neurochemical changes in adolescent (PND 37) and young adult (PND 58) rats. The results showed that chronic MDMA caused hippocampal protein deficits in adolescent and young adult rats at different levels: (1) impaired serotonergic (5-HT2A and 5-HT2C post-synaptic receptors) and GABAergic (GAD2 enzyme) signaling, and (2) decreased structural cytoskeletal neurofilament proteins (NF-H, NF-M and NF-L). Interestingly, these effects were not accompanied by an increase in apoptotic markers. In fact, chronic MDMA inhibited proteins of the apoptotic pathway (i.e., pro-apoptotic [[FADD]], Bax and cytochrome c) leading to an inhibition of cell death markers (i.e., p-JNK1/2, cleavage of PARP-1) and suggesting regulatory mechanisms in response to the neurochemical changes caused by the drug. The data, together with the observed lack of [[GFAP]] activation, support the view that chronic MDMA effects, regardless of the rat developmental age, extends beyond neurotransmitter systems to impair other hippocampal structural cell markers. Interestingly, inhibitory changes in proteins from the apoptotic pathway might be taking place to overcome the protein deficits caused by MDMA.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Apoptosis
* Body Temperature
* Body Weight
* Cytochromes c
* Down-Regulation
* Fatty Acid Desaturases
* Glutamate Decarboxylase
* Hallucinogens
* Hippocampus
* Male
* N-Methyl-3,4-methylenedioxyamphetamine
* Neurofilament Proteins
* Rats
* Rats, Sprague-Dawley
* Receptor, Serotonin, 5-HT2A
* Receptor, Serotonin, 5-HT2C
* Signal Transduction
* bcl-2-Associated X Protein
|keywords=* Adolescence
* FADD
* Hippocampus
* MDMA
* Neuroplasticity
|full-text-url=https://sci-hub.do/10.1016/j.neuro.2015.06.001
}}
{{medline-entry
|title=The Heart Protection Effect of Alcalase Potato Protein Hydrolysate Is through [[IGF1R]]-PI3K-Akt Compensatory Reactivation in Aging Rats on High Fat Diets.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25950762
|abstract=The prevalence of obesity is high in older adults. Alcalase potato protein hydrolysate (APPH), a nutraceutical food, might have greater benefits and be more economical than hypolipidemic drugs. In this study, serum lipid profiles and heart protective effects were evaluated in high fat diet (HFD) induced hyperlipidemia in aging rats treated with APPH (15, 45 and 75 mg/kg/day) and probucol (500 mg/kg/day). APPH treatments reduced serum triacylglycerol (TG), total cholesterol (TC), and low density lipoprotein (LDL) levels to the normal levels expressed in the control group. Additionally, the [[IGF1R]]-PI3K-Akt survival pathway was reactivated, and Fas-[[FADD]] (Fas-associated death domain) induced apoptosis was inhibited by APPH treatments (15 and 45 mg/kg/day) in HFD aging rat hearts. APPH (75 mg/kg/day) rather than probucol (500 mg/kg/day) treatment could reduce serum lipids without affecting HDL expression. The heart protective effect of APPH in aging rats with hyperlipidemia was through lowering serum lipids and enhancing the activation of the compensatory [[IGF1R]]-PI3K-Akt survival pathway. 
|mesh-terms=* Aging
* Animals
* Anticholesteremic Agents
* Apoptosis
* Cardiotonic Agents
* Cholesterol
* Diet, High-Fat
* Dietary Supplements
* Fas-Associated Death Domain Protein
* Hyperlipidemias
* Lipoproteins, LDL
* Phosphatidylinositol 3-Kinases
* Plant Proteins
* Probucol
* Protein Hydrolysates
* Proto-Oncogene Proteins c-akt
* Rats
* Rats, Sprague-Dawley
* Receptor, IGF Type 1
* Signal Transduction
* Solanum tuberosum
* Subtilisins
* Triglycerides

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463638
}}
{{medline-entry
|title=TNF/TNFR₁ pathway and endoplasmic reticulum stress are involved in ofloxacin-induced apoptosis of juvenile canine chondrocytes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24582689
|abstract=Quinolones cause obvious cartilaginous lesions in juvenile animals by chondrocyte apoptosis, which results in the restriction of their use in pediatric and adolescent patients. Studies showed that chondrocytes can be induced to produce TNFα, and the cisternae of the endoplasmic reticulum in quinolone-treated chondrocytes become dilated. We investigated whether TNF/TNFR₁ pathway and endoplasmic reticulum stress (ERs) are involved in ofloxacin (a typical quinolone)-induced apoptosis of juvenile canine chondrocytes. Canine juvenile chondrocytes were treated with ofloxacin. Cell survival and apoptosis rates were determined with MTT method and flow cytometry, respectively. The gene expression levels of the related signaling molecules (TNFα, TNFR₁, [[TRADD]], [[FADD]] and caspase-8) in death receptor pathways and main apoptosis-related molecules (calpain, caspase-12, GADD153 and GRP78) in ERs were measured by qRT-PCR. The gene expression of TNFR₁ was suppressed with its siRNA. The protein levels of TNFα, TNFR₁ and caspase-12 were assayed using Western blotting. The survival rates decreased while apoptosis rates increased after the chondrocytes were treated with ofloxacin. The mRNA levels of the measured apoptosis-related molecules in death receptor pathways and ERs, and the protein levels of TNFα, TNFR₁ and caspase-12 increased after the chondrocytes were exposed to ofloxacin. The downregulated mRNA expressions of TNFR₁, Caspase-8 and [[TRADD]], and the decreased apoptosis rates of the ofloxacin-treated chondrocytes occurred after TNFR₁-siRNA interference. Ofloxacin-induced chondrocyte apoptosis in a time- and concentration-dependent fashion. TNF/TNFR₁ pathway and ERs are involved in ofloxacin-induced apoptosis of juvenile canine chondrocytes in the early stage.
|mesh-terms=* Aging
* Animals
* Anti-Bacterial Agents
* Apoptosis
* Caspase 12
* Cells, Cultured
* Chondrocytes
* Dogs
* Dose-Response Relationship, Drug
* Endoplasmic Reticulum Stress
* Ofloxacin
* RNA, Messenger
* Receptors, Tumor Necrosis Factor, Type I
* Signal Transduction
* Tumor Necrosis Factor-alpha
|keywords=* Apoptosis
* Canine chondrocytes
* Endoplasmic reticulum stress
* Ofloxacin
* Quinolones
* TNF/TNFR(1) pathway
|full-text-url=https://sci-hub.do/10.1016/j.taap.2014.02.003
}}
{{medline-entry
|title=Epigallocatechin-3-gallate improves plantaris muscle recovery after disuse in aged rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24316035
|abstract=Aging exacerbates muscle loss and slows the recovery of muscle mass and function after disuse. In this study we investigated the potential that epigallocatechin-3-gallate (EGCg), an abundant catechin in green tea, would reduce signaling for apoptosis and promote skeletal muscle recovery in the fast plantaris muscle and the slow soleus muscle after hindlimb suspension (HLS) in senescent animals. Fischer 344 × Brown Norway inbred rats (age 34 months) received either EGCg (50 mg/kg body weight), or water daily by gavage. One group of animals received HLS for 14 days and a second group of rats received 14 days of HLS, then the HLS was removed and they recovered from this forced disuse for 2 weeks. Animals that received EGCg over the HLS followed by 14 days of recovery, had a 14% greater plantaris muscle weight (p<0.05) as compared to the animals treated with the vehicle over this same period. Plantaris fiber area was greater after recovery in EGCg (2715.2±113.8 μm(2)) vs. vehicle treated animals (1953.0±41.9 μm(2)). In addition, activation of myogenic progenitor cells was improved with EGCg over vehicle treatment (7.5% vs. 6.2%) in the recovery animals. Compared to vehicle treatment, the apoptotic index was lower (0.24% vs. 0.52%), and the abundance of pro-apoptotic proteins Bax (-22%), and [[FADD]] (-77%) was lower in EGCg treated plantaris muscles after recovery. While EGCg did not prevent unloading-induced atrophy, it improved muscle recovery after the atrophic stimulus in fast plantaris muscles. However, this effect was muscle specific because EGCg had no major impact in reversing HLS-induced atrophy in the slow soleus muscle of old rats.
|mesh-terms=* Aging
* Animals
* Apoptosis
* Body Weight
* Catechin
* Drug Evaluation, Preclinical
* Glycogen Synthase Kinase 3
* Glycogen Synthase Kinase 3 beta
* Hindlimb Suspension
* Isometric Contraction
* Muscle Fibers, Skeletal
* Muscle, Skeletal
* Muscular Atrophy
* Organ Size
* Proto-Oncogene Proteins c-akt
* Rats
* Rats, Inbred BN
* Rats, Inbred F344
* Signal Transduction
* Stem Cells
* Weight-Bearing
|keywords=* Apoptosis
* Catechin
* Muscle atrophy
* Muscle fiber area
* Muscle function
* Sarcopenia
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072042
}}
{{medline-entry
|title=A critical role of Fas-associated protein with death domain phosphorylation in intracellular reactive oxygen species homeostasis and aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24295239
|abstract=Reactive oxygen species (ROS) plays important roles in aging. However, the specific mechanisms for intracellular ROS accumulation, especially during aging, remain elusive. We have reported that Fas-associated protein with death domain ([[FADD]]) phosphorylation abolishes the recruitment of phosphatase type 2A C subunit (PP2Ac) to protein kinase C (PKC)βII, which specifically regulates mitochondrial ROS generation by p66shc. Here, we have studied the role of [[FADD]] phosphorylation in an [[FADD]] constitutive-phosphorylation mutation ([[FADD]]-D) mouse model. In [[FADD]]-D mice, the constitutive [[FADD]] phosphorylation led to ROS accumulation (hydrogen peroxide [H₂O₂]), in a process that was dependent on PKCβ and accompanied by increased PKCβ and p66shc phosphorylation, impaired mitochondrial integrity, and enhanced sensitivity to oxidative stress-mediated apoptosis. Moreover, [[FADD]]-D mice exhibited premature aging-like phenotypes, including DNA damage, cellular senescence, and shortened lifespan. In addition, we demonstrate that [[FADD]] phosphorylation and the recruitment of PP2A and [[FADD]] to PKCβ are induced responses to oxidative stress, and that the extent of [[FADD]] phosphorylation in wild-type mice was augmented during aging, accompanied by impairment of the interaction between PKCβ and PP2A. The present study first addresses the role of [[FADD]] phosphorylation in aging through controlling mitochondrial ROS specifically generated by PKCβ. These data identify that [[FADD]] phosphorylation is critical for the PKCβ-p66shc signaling route to generate H₂O₂ and to implicate enhanced [[FADD]] phosphorylation as a primary cause of ROS accumulation during aging.
|mesh-terms=* Aging
* Animals
* Cell Proliferation
* Cells, Cultured
* Fas-Associated Death Domain Protein
* Immunohistochemistry
* Immunoprecipitation
* In Situ Nick-End Labeling
* Male
* Mice
* Phosphorylation
* Reactive Oxygen Species
* Reverse Transcriptase Polymerase Chain Reaction

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048578
}}