Редактирование: BECN1 (раздел)

==Publications==

{{medline-entry
|title=Calpain-dependent Beclin1 cleavage stimulates senescence-associated cell death in HT22 hippocampal cells under the oxidative stress conditions.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30807795
|abstract=Oxidative damage in neurons including glutamate excitotoxicity has been linked to increasing numbers of neuropathological conditions. Under these conditions, cells trigger several different cellular responses such as autophagy, apoptosis, necrosis and senescence. However, the connection between these responses is not well understood. In this study, we found that the 60-kDa [[BECN1]] was specifically degraded to a 40-kDa fragment in hippocampal HT22 cells treated with 5 mM glutamate. Increased [[BECN1]] cleavage was specifically associated with a decrease in cell viability under oxidative stress. Interestingly, this [[BECN1]] cleavage was specifically inhibited by a calpain inhibitor ALLN but was not affected by other protease inhibitors. Also, the [[BECN1]] cleavage was not detected in calpain-4-deficient cell lines. Furthermore, calpain cleaved [[BECN1]] at a specific site between the coiled-coil domain and Bcl2 homology 3 domain, which is associated with the anti-apoptotic protein Bcl-2. Moreover, some cellular senescence markers, including β-galactosidase, p21, p27 , p53 and p16 , increased proportionally to those of [[BECN1]] cleaved fragments. These results suggest that calpain-mediated [[BECN1]] cleavage under oxidative conditions is specifically associated with cell death induced by cellular senescence.
|mesh-terms=* Animals
* Apoptosis
* Beclin-1
* Calpain
* Caspases
* Cell Line
* Cell Survival
* Cellular Senescence
* Glutamic Acid
* HeLa Cells
* Hippocampus
* Humans
* Leupeptins
* Mice
* NIH 3T3 Cells
* Neurons
* Oxidative Stress
* Reactive Oxygen Species
|keywords=* BECN1
* Calpain
* Glutamate excitotoxicity
* Oxidative stress
* Senescence
|full-text-url=https://sci-hub.do/10.1016/j.neulet.2019.02.036
}}
{{medline-entry
|title=Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR-[[ULK1]] signaling pathway.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29344647
|abstract=Presbycusis is the most common sensory impairment associated with aging; however, the underlying molecular mechanism remains unclear. Autophagy has been demonstrated to serve a key role in diverse diseases; however, no studies have examined its function in central presbycusis. The aim of the present study was to investigate the changes of autophagy in the physiological processes of the auditory cortex and its role in the degeneration of the auditory cortex, as well as the related mechanisms using naturally aging rats and a D‑galactose (D‑gal)‑induced mimetic rat model of aging. The present study demonstrated that autophagy increased from 3 months to 15 months in the normal saline (NS) control group, while it decreased in the D‑gal group. Compared with the age‑matched NS group, the D‑gal group demonstrated significantly increased levels of the autophagy‑related proteins, LC3 and Beclin 1 ([[BECN1]]) and the anti‑apoptotic proteins B‑cell lymphoma (BCL)2 and BCL‑extra large (BCL‑xL) at 3 months, with no obvious changes in cell apoptosis level and neuron ultrastructural morphology. However, LC3, [[BECN1]], [[BCL2]] and BCL‑xL were decreased at 15 months in the D-gal group, with cell apoptosis significantly increased and substantial neuron degeneration. Additionally, 5' AMP‑activated protein kinase (AMPK) activity was enhanced, and mechanistic target of rapamycin (mTOR) and [[ULK1]] phosphorylation (Ser 757) activities were inhibited at 3 months compared with those of the NS group, while the opposite was observed at 9 and 15 months. The present results suggested that autophagy increases from young to adult and decreases at old age in the physiological processes of the auditory cortex, and has anti‑apoptotic as well as anti‑aging functions in the degeneration of the auditory cortex. Additionally, autophagy was regulated through AMPK activation and mTOR suppression, and impairment of autophagy may serve a key role in the degeneration of the auditory cortex, even in the pathogenesis of central presbycusis.
|mesh-terms=* AMP-Activated Protein Kinases
* Aging
* Animals
* Apoptosis
* Auditory Cortex
* Autophagy
* Autophagy-Related Protein-1 Homolog
* Male
* Rats, Sprague-Dawley
* Signal Transduction
* TOR Serine-Threonine Kinases

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810242
}}
{{medline-entry
|title=Metabolomic analyses reveal that anti-aging metabolites are depleted by palmitate but increased by oleate in vivo.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26098646
|abstract=Recently, we reported that saturated and unsaturated fatty acids trigger autophagy through distinct signal transduction pathways. Saturated fatty acids like palmitate (PA) induce autophagic responses that rely on phosphatidylinositol 3-kinase, catalytic subunit type 3 ([[PIK3C3]], best known as VPS34) and beclin 1 ([[BECN1]]). Conversely, unsaturated fatty acids like oleate (OL) promote non-canonical, [[PIK3C3]]- and [[BECN1]]-independent autophagy. Here, we explored the metabolic effects of autophagy-inducing doses of PA and OL in mice. Mass spectrometry coupled to principal component analysis revealed that PA and OL induce well distinguishable changes in circulating metabolites as well as in the metabolic profile of the liver, heart, and skeletal muscle. Importantly, PA (but not OL) causes the depletion of multiple autophagy-inhibitory amino acids in the liver. Conversely, OL (but not PA) increased the hepatic levels of nicotinamide adenine dinucleotide (NAD), an obligate co-factor for autophagy-stimulatory enzymes of the sirtuin family. Moreover, PA (but not OL) raised the concentrations of acyl-carnitines in the heart, a phenomenon that perhaps is linked to its cardiotoxicity. PA also depleted the liver from spermine and spermidine, 2 polyamines have been ascribed with lifespan-extending activity. The metabolic changes imposed by unsaturated and saturated fatty acids may contribute to their health-promoting and health-deteriorating effects, respectively. 
|mesh-terms=* Aging
* Amino Acids
* Animals
* Autophagy
* Female
* Liver
* Mass Spectrometry
* Metabolomics
* Mice
* Mice, Inbred C57BL
* Muscle, Skeletal
* Myocardium
* NAD
* Oleic Acid
* Palmitates
* Phosphatidylinositol 3-Kinases
* Principal Component Analysis
* Signal Transduction
* Spermidine
* Spermine
|keywords=* NAD sirtuins
* aging
* amino acids
* autophagy
* spermidine
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615103
}}