Molecular Mechanisms of Training Effects
Atko Viru in Adaptation in Sports Training, 2017
The link between protein degradation and the subsequent protein synthesis may be specific or unspecific. The specific link means that inductors for adaptive protein synthesis are produced as a result of protein degradation. This would suggest that balanced protein turnover is achieved by the influence of protein metabolites on the genes whose expression is the synthesis of degraded proteins. If the same mechanism provides the adaptive increase in protein content, the training-induced development of both protein structures and enzyme systems must be related to the inductor-action of some products of protein breakdown. The unspecific links may be founded on the production of inductors in other metabolic processes that take place simultaneously with but independently of protein degradation.
Proteasome and Protease Inhibitors
Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey in Innovative Leukemia and Lymphoma Therapy, 2019
The proteasome is present in both the cytoplasm and nucleus of cells (24,25). The 26S proteasome is a large intracellular protease (l,500–2,000kDa) that consists of a 20S core catalytic complex and two 19S regulatory subunits (26–28). The 20S proteasome complex is a macromolecule of 700 kDa, made up of four stacked rings. The two outer rings contain seven α-subunits, while the two inner rings consist of seven β-subunits. The β1, 2, and 5 subunits contain the postglutamyl peptidyl hydrolytic-, tryptic-, and chymotryptic-like proteolytic activities of the proteasome, respectively (26,27,29). Together, these three can hydrolyze almost all peptide bonds of proteins, thus forming smaller polypeptide units. When combined with the two 19S regulatory units, the 26S proteasome is formed. This form of the proteasome is the most important mediator of protein degradation.
HIV and Aging
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
HIV may affect proteostasis, the ability of an organism to maintain the balance of cellular and extracellular proteins and peptides by correcting abnormal protein folding or degrading dysfunctional proteins by processes such as autophagy. There is evidence that HIV itself can both inhibit and enhance autophagy in immune cells (T cells and macrophages), depending on the cell type [70,71]. These effects on autophagy are a direct result of HIV viral proteins such as env, vif, and tat. This disruption of the normal protein degradation processes theoretically could affect cellular function and accelerate aging.
Circadian regulation of cardiac muscle function and protein degradation
Published in Chronobiology International, 2023
Proteostasis, including protein synthesis, processing/folding and degradation, is an important cellular mechanism in cardiac muscles (Henning and Brundel 2017; McLendon and Robbins 2015). Compared with non-muscle cells, cardiac muscles are terminally differentiated, must contract throughout lifetime, require robust metabolic/stress responses and involve specialized cellular machineries for electric conductance. The structural and functional unit of striated muscles, including both cardiac and skeletal muscles, is the sarcomere (Martin and Kirk 2020; Ono 2010), which is highly conserved throughout from worms to mammals. Sarcomeres line up sequentially, and tied together by a complex protein assembly called Z-disc to form contractible myofibrils, which in turn are bound in bundles to form cardiomyocytes. The sarcomere consists mainly of the myosin thick filaments and actin thin filaments, with a large number of associated structural and regulatory proteins. Given the heart is the first organ to be formed after birth and must continuously function until death, and that cardiomyocytes are post-mitotic, protein quality control at the sarcomere plays a particularly important role in cardiac proteostasis (Henning and Brundel 2017; Martin and Kirk 2020). Of particular importance is protein degradation mechanisms to remove misfolded or faulty proteins.
Proteomics and pulse azidohomoalanine labeling of newly synthesized proteins: what are the potential applications?
Published in Expert Review of Proteomics, 2018
Excess proteins are not only a burden for cells, but also a waste of cellular energy. The degradation of NSPs is an extremely important component of proteostasis as well as the removal of aged or damaged proteins. Protein degradation is mediated by two major pathways, the ubiquitin-proteasome pathway and lysosomal proteolysis. Autophagy is a highly conserved intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Under normal conditions, autophagy occurs constitutively at basal levels, possibly reflecting its role in the degradation of long-lived proteins and the removal of damaged cellular organelles [85]. Under stress such as starvation, enhanced autophagy flux promotes dynamic recycling of the basic biomolecules such as amino acids [86]. Autophagy is a dynamic process and has been implicated in pathological conditions including neurodegenerative diseases, cancer, and inflammatory diseases [87,88]. Modulation of autophagy has become a potentially interesting therapeutic target in human diseases, which makes it essential to provide evidence and information for altered autophagy. AHA has been used in recent studies to trace the autophagic flux [89]. After a click reaction between an azide and an alkyne, the azide-containing proteins can be detected with an alkyne-tagged fluorescent dye, coupled with flow cytometry. In this way, global protein degradation can be quantitatively detected during autophagic flux by calculating fluorescence intensity. To provide more details, MS-based AHA quantification strategies could be used to measure individual proteins.
Exosomes derived from HeLa cells break down vascular integrity by triggering endoplasmic reticulum stress in endothelial cells
Published in Journal of Extracellular Vesicles, 2020
Yinuo Lin, Chi Zhang, Pingping Xiang, Jian Shen, Weijian Sun, Hong Yu
Protein degradation via lysosome and ubiquitin/proteasome system are two routine pathways for cellular protein degradation. Interestingly, autophagy was observed in ECs after treated with ExoHeLa. Several studied have demonstrated that TJ proteins can be degraded by autophagy/lysosome and ubiquitin/proteasome [36–39]. For example, Wang et al. showed that particulate matter (PM) exposure could induce ZO-1 relocation from the cell periphery into lysosome, accompanied by significant reductions in ZO-1 protein levels, which required calpain activation [40]. Human immunodeficiency virus (HIV)-1 protein gp120 is also implicated as a cause of the breakdown of TJs between ECs due to increased degradation of ZO-1 and ZO-2 by proteasome [41]. In our study, we tried to clarify whether ExoHeLa down-regulates the TJs due to the enhanced protein degradation via autophagy/lysosome and ubiquitination/proteasome pathway. It has been reported that MG-132, a proteasome inhibitor effective for the lysosomal proteases [42], can inhibit the ubiquitination of CLDN5 [26]. However, our results indicated that inhibition of proteasome by MG132 cannot stop the reduction of TJ proteins in ExoHeLa-treated HUVECs. Furthermore, neither PI3K-type III inhibitor 3-MA, which inhibits the initiation of autophagy [43] nor CQ, an autophagy inhibitor via inhibition of the acidification of lysosomes [44], could restore the TJ proteins. These findings imply that neither autophagy/lysosome nor ubiquitination/proteasome pathway is responsible for the down-regulation of TJs in ExoHeLa-treated ECs.