Impact of Dietary Polyphenols on Arterial Stiffness
Catherina Caballero-George in Natural Products and Cardiovascular Health, 2018
Autophagy is a complex cellular process. It starts with the sequestration of cytoplasmic constituents into double-membraned vesicles, termed autophagosomes. Fusion of autophagosomes with lysosomes results in the degradation of the incorporated material into amino acids, carbohydrates, fatty acids and nucleotides. Through the recycling of biomolecules, basal autophagy provides new building blocks to support cellular function and homeostasis, as a response to stressful stimuli (e.g. accumulation of damaged organelles, nutrient deprivation, hypoxia). It is therefore a cytoprotective process involved in such diseases as cardiovascular disease, cancer and neurodegenerative disorders. However, little is known about autophagy in arterial ageing and vascular stiffness. Normally, autophagy preserves endothelial function, and age-related impaired autophagy contributes to arterial stiffness and endothelial dysfunction associated with increased levels of oxidative stress and inflammation (De Meyer et al., 2015; Sasaki et al., 2017).
Urinary System
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
Autophagy is a recently described phenomenon that not only occurs in several cell types as a normal physiologic process, but also has been associated with apoptosis and necrosis in some types of renal injury. During autophagy, a portion of cytoplasm is enveloped in double membrane-bound structures called autophagosomes, which undergo maturation and fusion with lysosomes for degradation, where these processes appear to be dependent on the upregulation of a specific family of genes called Atg (Periyasamy-Thandavan et al. 2009). It appears that autophagy is a general cellular response to stress and has been demonstrated with cisplatinin and cyclosporine toxicity in the kidney. Depending on experimental conditions, autophagy can directly induce cell death or act as a mechanism of cell survival and actually be cytoprotective against further injury, in association with other cell survival genes such as p21. The eventual cellular outcome in AKI (necrosis vs. regeneration) is, therefore, dependent on whether these and other prosurvival cytoprotective pathways can counterbalance the coincidental cellular signals promoting cell death, and this may depend on whether there is further exposure to the toxicant.
Mitochondrial Oxidative Stress in Aging and Healthspan
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
Several cellular mechanisms are involved in proteostasis and protein quality control. Autophagy is one of the main mechanisms degrading the vast majority of proteins. The other mechanism includes ubiquitin–proteasome pathway. Autophagic degradation involves lysosomes, which contains several digestive enzymes.39 Three major pathways have been described based on the delivery mechanisms of macromolecules to the lysosome: microautophagy, macroautophagy, and chaperone-mediated autophagy (CMA).40 Microautophagy acts through invaginations of the lysosomal membrane directly engulfing cytoplasmic macromolecules into the lysosome followed by enzymatic degradation.40,41 Macroautophagy involves formation of autophagosomes, which are double-membrane vesicles formed by phagophores engulfing cytosolic proteins and organelles. These autophagosomes fuse with lysosomes, leading to the degradation of the sequestered cellular contents by lysosomal enzymes.42,43 CMA is a targeted degradation, in which cytosolic proteins containing a pentapeptide KFERQ motif are targeted and translocated across the lysosomal membrane, resulting in the degradation of specific proteins.44 These three mechanisms of autophagy may occur simultaneously in various cell types.39,45,46 Macroautophagy is the most extensively studied of these three mechanisms and will be the focus of the following discussion.
Biosynthesis of silver nanoparticles using Citrus hystrix leaf extract and evaluation of its anticancer efficacy against HeLa cell line
Published in Drug Development and Industrial Pharmacy, 2022
Swetha Srimurugan, Anjali K. Ravi, Vijaya Anand Arumugam, Saradhadevi Muthukrishnan
Cervical cancer persists as the second major malignancy among women, with an annual global incidence of 570,000 diagnosed cases and 311,000 fatalities [1]. Human papilloma virus (HPV) infection is regarded as the major causative agent for the development of cervical cancer. Other risk factors include poor hygiene conditions, smoking, oral contraceptive usage, lifestyle changes, lack of physical activity, and exposure to radiation [2]. Since the inadequate preventive screening methods and early diagnosis, cervical cancer becomes aggressive and metastasizes into various parts [3]. The autophagy and apoptosis pathways maintain cellular homeostasis, but cancer cells become resistant to these pathways via modifying the anti and pro-apoptotic proteins to induce proliferation and metastasis of cancer cells [4]. Autophagy is a dynamic process associated with the formation of autophagosome, a double-membrane cytoplasmic vesicle which engulfs the damaged cellular components. The autophagosome can combine with lysosomes to generate auto-lysosomes, which preferentially destroy damaged cellular organelles and proteins by interacting with phosphatidyl ethanolamine, ATG 3, and ATG7 [5]. In normal circumstances, Beclin1 initiates autophagy by recruiting several autophagy-related complex proteins involved in autophagosome initiation and elongation. These protein complexes attract LC-3 I, which then transforms into LC-3 II [6].
Identification of a new structural family of SGK1 inhibitors as potential neuroprotective agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Ines Maestro, Enrique Madruga, Patricia Boya, Ana Martínez
In addition, the role of SGK1 in autophagy is being explored9. Autophagy is a degradative process, by which cytoplasmic content is sequestered in a double-membrane structure, called autophagosome. The autophagosome will fuse with lysosomes, where the cargo is degraded18. As mTORC2 participates in SGK1 activation and inhibits autophagy19, SGK1 could be considered as a negative regulator of the pathway20. In fact, autophagy was upregulated in muscle in SGK1-deficient mice21. Thus, the inhibition of the kinase by the compound GSK650394 induced autophagy22,23. However, a recent work done in HEI-OC1, a mouse auditory cell line, showed an upregulation of SGK1 and autophagy when cells were treated with caffeine. This event was inhibited when cells were co-treated with the inhibitor GSK65039424. Thus new studies are needed to unravel the autophagy modulation by SGK1.
Silver nanoparticles induce protective autophagy via Ca2+/CaMKKβ/AMPK/mTOR pathway in SH-SY5Y cells and rat brains
Published in Nanotoxicology, 2019
Lin Li, Lu Li, Xuejiao Zhou, Yang Yu, Zengqiang Li, Daiying Zuo, Yingliang Wu
Several pathways seem to regulate autophagy in mammalian cells. mTOR has been established as one of the key players regulating autophagy during cellular stress, and its inactivation is necessary for autophagy to occur (Jung et al. 2010). Under normal conditions, mTOR interacts with the ULK-ATG13-FIP200 complex to prevent ULK activation by phosphorylating ULK Ser 757 (p-ULKSer757), which suppresses autophagy. Conversely, when this complex is activated, for example, by rapamycin or AMPK, mTOR-mediated inhibitory p-ULKSer757 was significantly increased, which could cause Beclin-1 activation and autophagy (Meijer and Codogno 2004; Kim et al. 2011). Subsequently, Beclin-1 promotes lipidation of LC3-I to generate its lipidated form, LC3-II, which localizes to the autophagosome membrane to promote autophagosome formation. After formation, autophagosomes are capable of delivering proteins and organelles to lysosomes for degradation. Our present data showed that downregulation of mTOR and upregulation of p-ULK were significantly induced by AgNPs compared with the control. Furthermore, to confirm the influence of AMPK in AgNP-induced autophagy, the presence of dorsomorphin, an AMPK activity-specific inhibitor, remarkably increased the level of mTOR and decreased levels of p-ULK, Beclin-1, and the LC3-II/LC3-I expression ratio. Collectively, these data indicate that AgNP-triggered autophagy is mTOR-dependent.
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