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Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
The S100 proteins are a family of low-molecular-weight (9–13 kDa), ubiquitously expressed vertebrate proteins. They are called S100 because of their solubility in a 100% saturated solution with ammonium sulfate at neutral pH, as discovered by B. W. Moore in 1965. Each of them has two calcium binding EF-hand motifs in the monomer and forms antiparallel homodimers and occasionally heterodimers within themselves (e.g., S100A8/A9) and other proteins. They are not enzymes, but they are calcium-activated molecular switches similar to calmodulin or troponin C. They have pleiotropic intracellular and extracellular functions, for example, proliferation, differentiation, migration, energy metabolism, Ca2+ homeostasis, inflammation, and cell death. There are at least 25 members of S100, and some of their specific functions include scavenging of ROS and NO (i.e., S100A8/A9), cytoskeleton assembly (e.g., S100A1, S100A4, S100A6, and S100A9), membrane protein docking and trafficking (e.g., S100A10 and S100A12), transcription regulation and DNA repair (e.g., S100A4, S100A11, S100A14, and S100B), cell differentiation (e.g., S100A6, S100A8/A9, and S100B), release of cytokines and antimicrobial agents (degranulation) (e.g., S100A8/A9, S100A12, and S100A13), muscle cell contractility (e.g., S100A1), cell growth and migration (e.g., S100A4, S100A8/A9, S100B, and S100P), and apoptosis (e.g., S100A6, S100A9, and S100B). The S100 proteins, once extracellular, are saturated with calcium and do not act as a calcium sensing switch, but can now scavenge other transition metal ions, for example, Zn, Cu, and Mn, which might be part of their antimicrobial action.
The applications of targeted delivery for gene therapies in hearing loss
Published in Journal of Drug Targeting, 2023
Melissa Jones, Bozica Kovacevic, Corina Mihaela Ionescu, Susbin Raj Wagle, Christina Quintas, Elaine Y. M. Wong, Momir Mikov, Armin Mooranian, Hani Al-Salami
S100 is a calcium binding protein which is found in the mammalian inner ear. Studies of S100A1 have found its expression in both supporting cells, being Deiters cells and phalangeal cells, as well as inner hair cells [81,82]. Sox2 is an HMG domain transcription factor which has several roles, including in the development of hair cells. Postnatally, Sox2 is limited in expression to supporting cells, however, this expression is found in multiple supporting cell types, including pillar cells, Deiters cells, inner phalangeal cells, and Hensen’s cells [83,84]. Prox1 is a homeodomain transcription factor, which is expressed in several cell types embryonically, including both hair cells and supporting cells. However, postnatally, Prox1 becomes localised to a particular subset of supporting cells, including the third row of Deiters cells [82,83].
Influence of timolol, benzalkonium-preserved timolol, and benzalkonium-preserved brimonidine on oxidative stress biomarkers in the tear film
Published in Cutaneous and Ocular Toxicology, 2020
Lech Sedlak, Weronika Wojnar, Maria Zych, Dorota Wyględowska-Promieńska
Oxidative stress is a condition in which substances with prooxiative properties outnumber those which possess antioxidative abilities27,28. Scientific literature suggests that oxidative stress is one of the contributors to the development of DED or ocular surface inflammation9. Since the eye is constantly exposed to oxidative stress-triggering environmental factors, UV radiation, pathogenic microorganisms or pollutants, there is an antioxidative defense system in the ocular surface29. Tear film, as a first barrier between the eye and external environment, also provides an antioxidative defense. In the tear film, there are both non-enzymatic and enzymatic antioxidants that protect the surface against the ROS. To non-enzymatic antioxidants in human tears ascorbic acid, uric acid, glutathione (GSH) as well as L-cysteine and L-tyrosine can be included16. Moreover, tear film assures antioxidative protection due to its proteins, such as lactoferrin and S100A proteins as well as antioxidative enzymes like SOD, GPx, or CAT29.
Potential targets of gene therapy in the treatment of heart failure
Published in Expert Opinion on Therapeutic Targets, 2018
Jakub Rosik, Bartosz Szostak, Filip Machaj, Andrzej Pawlik
S100A1 is the main member of the S100 family in cardiac cells. Its distribution is uneven, and the highest protein concentrations of S100A1 are located in the left ventricles of adult hearts [26,27]. S100A1 plays a pivotal role in the regulation of numerous other proteins in cardiomyocytes; for example, it interacts with SERCA2a in a calcium-dependent manner to increase protein levels and activity. Ryanodine receptors, which play a huge role in calcium circulation, are also regulated by S100A1. The protein improves calcium release from the sarcoplasmic reticulum. S100A1 also modifies L-type calcium channels and the sodium-calcium exchanger. Apart from regulating calcium circulation, S100A1 is also present in mitochondria and interacts with various mitochondrial enzymes. Its interaction with F1-ATPase in a calcium-dependent and pH-dependent manner leads to an increase in enzyme activity. As a result, ATP generation is enhanced, and cells expressing S100A1 tend to have higher ATP concentrations [10,27–32]. It was shown that levels of S100A1 protein were reduced in cells in a HF model. Therefore, knowing the immense influence of S100A1 on cardiac cell contractility, energetic homeostasis and calcium circulation, it has become a promising target for gene therapy [26,27,29,31–33].