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Molecular Pathology
Published in Burkhard Madea, Asphyxiation, Suffocation,and Neck Pressure Deaths, 2020
A unique study carried out by Legaz Pérez et al. [19] analysed the concentrations of metallic ions (Fe, Zn, Mg and Ca) and the expression of P-selectin and cathepsin D in skin ligature marks. They found that intradermal concentrations of Ca and Mg were higher than those of Fe and Zn, although there was no significant difference in the concentrations of Ca and Mg between uninjured skins and ligature marks. The Fe and Zn concentrations, however, were significantly elevated in ligature marks. Moreover, there were positive correlations between cathepsin D and Fe and between P-selectin and Fe. Low Fe levels were observed in the case of a negative expression for cathepsin D and P-selectin, whereas high levels of Fe were found in sections with strong immunoreactivity cathepsin D and P-selectin. No significant relationships were found between Ca, Mg and Zn and the expression of cathepsin D or P-selectin.
Dermal Fibroblast Function
Published in Brian J. Nickoloff, Dermal Immune System, 2019
Proteoglycans are degraded in stages.67 The core protein and link proteins are cleaved by the proteases, including cathepsin B.68 Glycosaminoglycan peptides and free proteoglycans are then pinocytosed by cells where they undergo further degradation in the lysosomes by cathepsins with acid pH optima of about 3, such as cathepsin D. Glycosaminoglycans are depolymerized by endoglycosidases and are further degraded by a variety of exoenzymes.69 Synthesis of proteoglycanase in fibroblasts is stimulated by IL-1α and -β and TNF-α.61
Mechanisms of Fibril Formation and Cellular Response
Published in Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin, XIth International Symposium on Amyloidosis, 2007
Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin
HMCs immunohistochemically stained for CD68 expression was markedly increased in those treated with AL-LCs compared to control and LCDD treated cells. Increased expressions of LAMP and cathepsin-D but not EEA were also noted in HMCs incubated with AL-LCs compared with LCDD-LC treated and control cells (Figure 1). In addition, the amounts of lysosomes harvested from the lysosomal fractions prepared from AL-LC treated HMCs were significantly higher compared to LCDD-LC treated and control cells. Immunofluorescence staining for cathepsin-D, Lamp and EEA were recapitulated in the lysosomal preparations. Immunochemical staining for the cathepsin enzymes showed increased expression of these enzymes in the AL-LC treated cells compared to controls. Immunoglold labeling demonstrated the presence of monoclonal amyloidogenic light chains in lysosomes in intact HMCs and in lysosomal fractions with associated fibrils (Figure 2).
Cardio-protective effects of terminalia catappa leaves and terminalia chebula fruit extract in doxorubicin-induced cardiomyopathy in rats
Published in Biomarkers, 2022
Ramasamy Manikandan, Balamuralikrishnan Balasubramanian, Panneerselvam Punniyakotti, Arumugam Vijaya Anand, Arun Meyyazhagan, Shanmugam Velayuthaprabhu, Rengasamy Lakshminarayanan Rengarajan, Utthapon Issara, Wen-Chao Liu
In the present study, the Tct.LE and Tce.FE, propranolol enhances the activities of TCA cycle enzymes, these may improve the mitochondrial antioxidant defence system and overcome the complications with the decreased TCA cycle function. The treatment with Tct.LE and Tce.FE, propranolol may reduce the oxidative damage in the mitochondria and enhances the antioxidant status. The decrease in mitochondrial antioxidants could be due to the feedback inhibition or oxidative inactivation of enzyme protein caused by the excess ROS generation (Al-Assaf 2014). Cathepsin D is a lysosomal enzyme, which is present in all animal cells (Sudharsan 2006). It is mainly involved in the autophagic digestion of discrete parts of the cytoplasm and the proteins present in the myofibrillary and mitochondria. This type of lysosomal enzymes stimulates the oxygen radical; it disturbs the cardiac tissues. These are in agreement with Suchalatha and Devi (2005), who reported that the levels of β-D-glucuronidase and β-N-acetyl glucosaminidase levels are reduced in the T. chebula treats in the isoproterenol-induced cardiac damage in rats.
Recent advances in proteolytic stability for peptide, protein, and antibody drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Xianyin Lai, Jason Tang, Mohamed E.H. ElSayed
For peptidases inside cells of various organs and tissues, many of them act on specific peptides and proteins. However, cathepsins are a special group of peptidases and have high concentrations in endosomes and lysosomes to breakdown peptides and proteins. Cathepsins provide a delicate balance of expression, targeting, zymogen activation, inhibition by protein inhibitors and degradation [80]. There are 15 cathepsins encoded in the human genome, including serine proteases A and G, cysteine proteases B, C, F, H, K, L, O, S, V, W, and X (or Z), and aspartyl proteases D and E. Among the cathepsins, cathepsin D (EC 3.4.23.5) is the most intensively studied and is the main endolysosome enzyme [81,82]. Therefore, cathepsin D is highly relevant to the evaluation of peptide, protein, and antibody drug proteolytic stability.
Aloe vera and Honey Solution and Their Ethanolic Extraction Solution Could Act on Metastasis-Regulating Processes in Walker 256 Tumor Tissues In Vivo?
Published in Nutrition and Cancer, 2021
Rebeka Tomasin, Aislan Cristina Rheder Fagundes Pascoal, Marcos José Salvador, Maria Cristina Cintra Gomes-Marcondes
In conclusion, this study has demonstrated that treatment with Aloe vera and honey solution (A) and their ethanolic fraction (F) could reduce the metastatic propensity of tumors by modulating neoangiogenesis and the process of epithelial-to-mesenchymal transition. An analysis of the primary tumor tissues of these animals showed a decrease in N-cadherin expression in groups WA and WF, with a concomitant increase in E-cadherin expression in group WA compared to the control group (W). Cathepsin D activity was also decreased in the tumor tissues from groups WA and WF. In addition, the number of blood vessels and their diameter significantly reduced in tumor tissues from groups WA and WF compared to those from group W. In the bioactive extracts were identified compounds with proven anti-tumor activity, such as caffeic acid, ferulic acid, mannose, aloin A, aloin B, pinocembrin, chrysin and kaempferol.