Редактирование: ATG12 (раздел)

==Publications==

{{medline-entry
|title=Lifelong Football Training: Effects on Autophagy and Healthy Longevity Promotion.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30837897
|abstract=Aging is a physiological process characterized by a progressive decline of biological functions and an increase in destructive processes in cells and organs. Physical activity and exercise positively affects the expression of skeletal muscle markers involved in longevity pathways. Recently, a new mechanism, autophagy, was introduced to the adaptations induced by acute and chronic exercise as responsible of positive metabolic modification and health-longevity promotion. However, the molecular mechanisms regulating autophagy in response to physical activity and exercise are sparsely described. We investigated the long-term adaptations resulting from lifelong recreational football training on the expression of skeletal muscle markers involved in autophagy signaling. We demonstrated that lifelong football training increased the expression of messengers: [[RAD23A]], [[HSPB6]], [[RAB1B]], [[TRAP1]], [[SIRT2]], and HSBPB1, involved in the auto-lysosomal and proteasome-mediated protein degradation machinery; of RPL1, [[RPL4]], [[RPL36]], MRLP37, involved in cellular growth and differentiation processes; of the Bcl-2, HSP70, HSP90, [[PSMD13]], and of the [[ATG5]]-[[ATG12]] protein complex, involved in proteasome promotion and autophagy processes in muscle samples from lifelong trained subjects compared to age-matched untrained controls. In conclusion, our results indicated that lifelong football training positively influence exercise-induced autophagy processes and protein quality control in skeletal muscle, thus promoting healthy aging.

|keywords=* autophagy
* cardiovascular capacity
* football
* lifelong training
* longevity
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390296
}}
{{medline-entry
|title=[[SIRT6]] histone deacetylase functions as a potential oncogene in human melanoma.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29234488
|abstract=Melanoma is an aggressive skin cancer that can rapidly metastasize to become fatal, if not diagnosed early. Despite recent therapeutic advances, management of melanoma remains difficult. Therefore, novel molecular targets and strategies are required to manage this neoplasm. This study was undertaken to determine the role of the sirtuin [[SIRT6]] in melanoma. Employing a panel of human melanoma cells and normal human melanocytes, we found significant [[SIRT6]] mRNA and protein upregulation in melanoma cells. Further, using a tissue microarray coupled with quantitative Vectra analysis, we demonstrated significant [[SIRT6]] overexpression in human melanoma tissues. Lentiviral short hairpin RNA-mediated knockdown of [[SIRT6]] in A375 and Hs 294T human melanoma cells significantly decreased cell growth, viability, and colony formation, induced G1-phase arrest and increased senescence-associated beta-galactosidase staining. As autophagy is important in melanoma and is associated with [[SIRT6]], we used a qPCR array to study [[SIRT6]] knockdown in A375 cells. We found significant modulation in several genes and/or proteins (decreases in [[AKT1]], [[ATG12]], [[ATG3]], [[ATG7]], [[BAK1]], [[BCL2L1]], [[CLN3]], [[CTSB]], [[CTSS]], [[DRAM2]], [[HSP90AA1]], [[IRGM]], [[NPC1]], [[SQSTM1]], [[TNF]], and BECN1; increases in [[GAA]], ATG10). Our data suggests that increased [[SIRT6]] expression may contribute to melanoma development and/or progression, potentially via senescence-and autophagy-related pathways.

|keywords=* SIRT6
* autophagy
* melanoma
* senescence
* sirtuins
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724804
}}
{{medline-entry
|title=Epigallocatechin-3-gallate increases autophagy signaling in resting and unloaded plantaris muscles but selectively suppresses autophagy protein abundance in reloaded muscles of aged rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28286171
|abstract=We have previously found that Epigallocatechin-3-gallate (EGCg), an abundant catechin in green tea, reduced apoptotic signaling and improved muscle recovery in response to reloading after hindlimb suspension (HS). In this study, we investigated if EGCg altered autophagy signaling in skeletal muscle of old rats in response to HS or reloading after HS. Fischer 344×Brown Norway inbred rats (age 34months) were given 1ml/day of purified EGCg (50mg/kg body weight), or the same sample volume of the vehicle by gavage. One group of animals received HS for 14days and the second group of rats received 14days of HS, then the HS was removed and they were allowed to recover by ambulating normally around the cage for two weeks. EGCg decreased a small number of autophagy genes in control muscles, but it increased the expression of other autophagy genes (e.g., [[ATG16L2]], [[SNCA]], [[TM9SF1]], Pink1, PIM-2) and HS did not attenuate these increases. HS increased Beclin1, [[ATG7]] and LC3-II/I protein abundance in hindlimb muscles. Relative to vehicle treatment, EGCg treatment had greater [[ATG12]] protein abundance (35.8%, P<0.05), but decreased Beclin1 protein levels (-101.1%, P<0.05) after HS. However, in reloaded muscles, EGCg suppressed Beclin1 and LC3-II/I protein abundance as compared to vehicle treated muscles. EGCg appeared to "prime" autophagy signaling before and enhance autophagy gene expression and protein levels during unloading in muscles of aged rats, perhaps to improve the clearance of damaged organelles. However, EGCg suppressed autophagy signaling after reloading, potentially to increase the recovery of hindlimb muscles mass and function after loading is restored.
|mesh-terms=* Aging
* Animal Nutritional Physiological Phenomena
* Animals
* Antioxidants
* Autophagy
* Catechin
* Hindlimb Suspension
* Male
* Muscle Fibers, Skeletal
* Muscle, Skeletal
* Muscular Atrophy
* Organ Size
* Rats
* Rats, Inbred BN
* Rats, Inbred F344
* Signal Transduction
|keywords=* Aging
* Autophagy
* Muscle reloading
* Muscle wasting
* Nutrition
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501279
}}
{{medline-entry
|title=Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28238968
|abstract=Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging. In skeletal muscle from aged mice, there also was a decline in LC3B-I conjugation to phosphatidylethanolamine (PE) possibly due to decreased protein levels of [[ATG3]] and [[ATG12]]-[[ATG5]]. The CMA markers, LAMP-2A and Hsc70, and mitochondrial turnover markers, Drp1, [[PINK1]] and PGC1α also were decreased. Metabolomics analysis showed impaired β-oxidation in heart of aged mice, whereas increased branched-chain amino acids (BCAAs) and ceramide levels were found in skeletal muscle of aged mice that in turn, may contribute to insulin resistance in muscle. Taken together, our studies showed similar declines in macroautophagy but distinct effects on CMA, mitochondrial turnover, and metabolic dysfunction in muscle [i]vs.[/i] heart during aging.
|mesh-terms=* Aging
* Animals
* Autophagy
* Biomarkers
* Energy Metabolism
* Lysosomes
* Mice
* Mitochondria
* Molecular Chaperones
* Muscle, Skeletal
* Myocardium
|keywords=* aging
* autophagy
* ceramide
* chaperone-mediated autophagy (CMA)
* fatty acid oxidation
* heart
* muscle
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361683
}}
{{medline-entry
|title=Autophagic homeostasis is required for the pluripotency of cancer stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27929731
|abstract=Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate-limiting enzyme in the NAD  synthesis pathway [[NAMPT]] (nicotinamide phosphoribosyltransferase) and the transcription factor [[POU5F1]]/OCT4 (POU class 5 homeobox 1). First, our data show that the pharmacological inhibition and knockdown (K ) of [[NAMPT]] or the K  of [[POU5F1]] in human CSCs significantly decreased the expression of pluripotency markers [[POU5F1]], [[NANOG]] (Nanog homeobox) and [[SOX2]] (SRY-box 2), and upregulated the differentiation markers [[TUBB3]] (tubulin β 3 class III), [[CSN2]] (casein β), [[SPP1]] (secreted phosphoprotein 1), [[GATA6]] (GATA binding protein 6), T (T brachyury transcription factor) and [[CDX2]] (caudal type homeobox 2). Interestingly, these pluripotency-regulating effects of [[NAMPT]] and [[POU5F1]] were accompanied by contrasting levels of autophagy, wherein [[NAMPT]] K  promoted while [[POU5F1]] K  inhibited the autophagy machinery. Most importantly, any deviation from the basal level of autophagy, either increase (via rapamycin, serum starvation or Tat-beclin 1 [Tat-BECN1] peptide) or decrease (via [[ATG7]] or [[ATG12]] K ), strongly decreased the pluripotency and promoted the differentiation and/or senescence of CSCs. Collectively, these results uncover the link between the NAD  biosynthesis pathway, CSC transcription factor [[POU5F1]] and pluripotency, and further identify autophagy as a novel regulator of pluripotency of CSCs.
|mesh-terms=* Animals
* Autophagy
* Beclin-1
* Cell Differentiation
* Cell Proliferation
* Cell Survival
* Cellular Senescence
* Cytokines
* Doxorubicin
* Homeostasis
* Mice
* Models, Biological
* Neoplastic Stem Cells
* Nicotinamide Phosphoribosyltransferase
* Octamer Transcription Factor-3
* PTEN Phosphohydrolase
* Phosphorylation
* Pluripotent Stem Cells
* Proto-Oncogene Proteins c-akt
* Signal Transduction
* Sirolimus
* TOR Serine-Threonine Kinases
|keywords=* POU5F1/Oct4
* autophagy
* cancer stem cells
* differentiation
* pluripotency
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324853
}}
{{medline-entry
|title=Macroautophagy is impaired in old murine brain tissue as well as in senescent human fibroblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27825071
|abstract=The overall decrease in proteolytic activity in aging can promote and accelerate protein accumulation and metabolic disturbances. To specifically analyze changes in macroautophagy (MA) we quantified different autophagy-related proteins (ATGs) in young, adult and old murine tissue as well as in young and senescent human fibroblasts. Thus, we revealed significantly reduced levels of [[ATG5]]-[[ATG12]], LC3-II/LC3-I ratio, Beclin-1 and p62 in old brain tissue and senescent human fibroblasts. To investigate the role of mTOR, the protein itself and its target proteins p70S6 kinase and 4E-BP1 were quantified. Significant increased mTOR protein levels were determined in old tissue and cells. Determination of phosphorylated and basal amount of both proteins suggested higher mTOR activity in old murine tissue and senescent human fibroblasts. Besides the reduced levels of ATGs, mTOR can additionally reduce MA, promoting further acceleration of protein accumulation and metabolic disturbances during aging.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Aging
* Animals
* Autophagy
* Autophagy-Related Proteins
* Brain
* Carrier Proteins
* Cell Cycle Proteins
* Cellular Senescence
* Down-Regulation
* Eukaryotic Initiation Factors
* Fibroblasts
* Gene Expression Regulation, Developmental
* Humans
* Male
* Mice
* Phosphoproteins
* Phosphorylation
* Ribosomal Protein S6 Kinases, 70-kDa
* TOR Serine-Threonine Kinases
|keywords=* ATGs
* Aging
* Autophagy-lysosome pathway
* Fibroblasts
* MTOR
* Senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099282
}}
{{medline-entry
|title=Follicle-stimulating hormone promotes age-related endometrial atrophy through cross-talk with transforming growth factor beta signal transduction pathway.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25393561
|abstract=It is widely believed that endometrial atrophy in postmenopausal women is due to an age-related reduction in estrogen level. But the role of high circulating follicle-stimulating hormone (FSH) in postmenopausal syndrome is not clear. Here, we explored the role of high circulating FSH in physiological endometrial atrophy. We found that FSH exacerbated post-OVX endometrial atrophy in mice, and this effect was ameliorated by lowering FSH with Gonadotrophin-releasing hormone agonist (GnRHa). In vitro, FSH inhibited endometrial proliferation and promoted the apoptosis of primary cultured endometrial cells in a dose-dependent manner. In addition, upregulation of caspase3, caspase8, caspase9, autophagy-related proteins (ATG3, ATG5, ATG7, [[ATG12]] and LC3) and downregulation of c-Jun were also observed in endometrial adenocytes. Furthermore, smad2 and smad3 showed a time-dependent activation in endometrial cells which can be partly inhibited by blocking the transforming growth factor beta receptor II (TβRII). In conclusion, FSH regulated endometrial atrophy by affecting the proliferation, autophagy and apoptosis of endometrial cells partly through activation of the transforming growth factor beta (TGFβ) pathway. 
|mesh-terms=* Age Factors
* Animals
* Atrophy
* Disease Models, Animal
* Endometrium
* Female
* Follicle Stimulating Hormone
* Humans
* Mice
* Signal Transduction
* Transforming Growth Factor beta
|keywords=* aging
* atrophy
* autophagy
* follicle-stimulating hormone
* menopause
* transforming growth factor beta
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364840
}}