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Diabetes Mellitus, Obesity, Lipoprotein Disorders and other Metabolic Diseases
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Lysosomes are cytoplasmic organelles which contain enzymes. Their major function is the degradation of macromolecules, but they are also involved in the uptake of molecules such as vitamin B12, lipoproteins, peptides, hormones and growth factors. Lysosomal storage diseases are rare and are usually autosomal recessive or X-linked recessive disorders. They are characterized by progressive deposition of metabolic substrates in organs including brain, liver, spleen and bone.
A Review on L-Asparaginase
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Numerous applications have been derived directly from enzymes because of their pharmaceutical properties. There are enzymes that have therapeutic uses, including L-arginase (antitumor); L-asparaginase (antitumor), L-tyrosinase (antitumor), L-glutaminase (antitumor), uricase (gout), urokinase (blood clots), glucosidase (antitumor), lysozyme (antibiotic), trypsin (inflammation), urokinase (anticoagulant), ribonuclease (antiviral), rhodanase (cyanide poisoning), hyaluronidase (heart attack), serratiopeptidase (anti-inflammatory), β-lactamase (penicillin allergy), dornase α (cystic fibrosis), collagenase (skin ulcers), streptokinase (anticoagulant), laccase (detoxifier), lipase (digest lipids), rasburicase (hyperuricemia), sacrosidase (congenital sucraseisomaltase deficiency) and peptidase (celiac disease). Currently, enzyme replacement therapy has been permitted for six lysosomal storage diseases, and rDNA human enzymes are under clinical trials (Kaur et al., 2012).
Signal transduction and exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Brendan Egan, Adam P. Sharples
In a similar manner to proteolysis, autophagy is likely to be involved in skeletal muscle remodelling in response to exercise. Autophagy occurs through various mechanisms that differ in the way they capture proteins or organelles and deliver them to the lysosome for degradation. Macro-autophagy involves entire regions of the cytosol or specific organelles and protein complexes being engulfed by a vacuole known as an autophagosome, which then fuses with the lysosome. Micro-autophagy involves the direct uptake of cytosolic components into lysosomes. In addition, more selective types of autophagy, known as chaperone-mediated autophagy and chaperone-assisted selective autophagy, are able to degrade specific proteins. Like the concept of protein degradation by the UPS, on first impression, autophagy may seem highly destructive, but autophagic processes are initiated by a single session of exercise (77), and in fact may be required for adaptation to exercise training (78). Conceptually, this can be thought of acute exercise activating signal transduction pathways that increase the turnover of skeletal muscle proteins (i.e. activation of both degradation and synthesis), and this increase in turnover is essential for the remodelling of cellular components such as contractile proteins and the extracellular matrix that occurs with exercise training.
Preclinical and clinical developments in enzyme-loaded red blood cells: an update
Published in Expert Opinion on Drug Delivery, 2023
Marzia Bianchi, Luigia Rossi, Francesca Pierigè, Sara Biagiotti, Alessandro Bregalda, Filippo Tasini, Mauro Magnani
Regarding enzyme replacement therapy approaches, several lines of evidence are accumulating in favor of loading therapeutic enzymatic proteins in EVs of different origin. For example, Liu et al. loaded catalase and glucose oxidase into macrophage-derived EVs for targeted photodynamic therapy in cancer [21]. Two further applications are found in the field of lysosomal storage disorders and are reported below. Do et al. loaded the enzyme β-glucocerebrosidase into engineered exosomes from different cell types for the treatment of the lysosomal Gaucher’s disease. They demonstrated that the enzyme was efficiently targeted to the endocytic compartments and exhibited significant activity into the recipient cell [126]. Haney and coworkers produced macrophage-derived EVs for brain delivery of the soluble lysosomal enzyme tripeptidyl peptidase-1, TPP1, to treat Batten disease [127]. Importantly, both groups transfected the ‘mother’ cells with enzyme-coding DNA and then isolated the enzyme-containing EVs produced by the cells.
Biodegradable hollow mesoporous organosilica nanotheranostics (HMONs) as a versatile platform for multimodal imaging and phototherapeutic-triggered endolysosomal disruption in ovarian cancer
Published in Drug Delivery, 2022
Pengfei Li, Bingquan Lin, Zhian Chen, Pan Liu, Jiaqi Liu, Weili Li, Ping Liu, Zhaoze Guo, Chunlin Chen
The lysosome is a crucial organelle – the digestive organ in cells (Zhu et al., 2017; Nakamura et al., 2019). Because of their strong degradation ability, lysosomes can remove cytotoxic substances, damaged or dead organelles, and mismatched proteins to maintain intracellular homeostasis (Mukherjee et al., 2019). Lysosomes also regulate intracellular signal transduction pathways. When the tumor microenvironment is hypoxic and undernourished, an alternative energy source is rapidly provided by degrading and recycling cellular components through lysosomes to meet the needs of cell growth and proliferation (Zhu et al., 2021). Therefore, tumor development and progression are closely related to the function of lysosomes, and triggering lysosome damage may be an effective method to induce tumor cell death.
Analysis of the acrylamide in breads and evaluation of mitochondrial/lysosomal protective agents to reduce its toxicity in vitro model
Published in Toxin Reviews, 2022
Ahmad Salimi, Rafat Pashaei, Shahab Bohlooli, Mehrdad Vaghar-Moussavi, Jalal Pourahmad
Lysosomes are the acidic organelles for recycling defective cellular and degradation materials and enable an optimal physicochemical environment for enzymatic activities, which need to be controlled (Pascua-Maestro et al.2017). Presently, documented functions like immune response, cell death, plasma membrane repair, energy, and nutrient sensing and secretion, reveal the importance of lysosomes in controlling fine decisions in the life of a cell (Xu and Ren 2015). Environmental tensions such as oxidative damages and ROS generation can damage lysosomal membranes and lead to membrane permeabilization. Usual function of lysosomes depends on intraluminal acidic pH and needs constant membrane-dependent proton gradients (Johansson et al.2010). Chloroquine agent prevents endosomal acidification. This drug accumulates inside the acidic parts of the cell, including lysosomes and endosomes. This accumulation leads to inhibition of lysosomal enzymes that require an acidic pH, and prevents fusion of endosomes and lysosomes. Moreover, chloroquine inhibits autophagy as it raises the lysosomal pH, which leads to inhibition of both fusion of autophagosome with lysosome and lysosomal protein degradation (Choi et al.2013). Our results showed that acrylamide induces lysosomal damages in human lymphocytes that their damage is prevented by chloroquine.