Disruptions in physical substrates of vision following traumatic brain injury
Mark J. Ashley, David A. Hovda in Traumatic Brain Injury, 2017
The brain has two solid components and four anatomical parts. The two core components are the gray matter and the white matter. Gray matter can be likened to a series of computers with the white matter being the wiring connecting them to one another. The major component of the gray matter includes neuronal cell bodies, called neurons. They have cellular extensions called dendrites and axons (the latter both myelinated and unmyelinated). Neurons are electrically polarized cells that specialize for conductance of electrical impulses projected down the axons and transmitted chemically over spaces called synapses to the dendrites of the next neuron. Electrical connectivity of large groups of neurons is termed brain circuitry. Besides intercellular connectivity, there is also intracellular connectivity, referred to as transduction. This total transfer of information is called cell signaling.
Oxidative Stress: Relevance, Evaluation, and Management
Botros Rizk, Ashok Agarwal, Edmund S. Sabanegh in Male Infertility in Reproductive Medicine, 2019
Phenolic compounds intake particularly is associated with reduced CVD, T2DM, and various malignancies. However, the molecular mechanisms are complex, mediated through numerous different pathways directly and indirectly. This may include gene modulation and transcription factor regulation in various cell-signaling cascades, particularly involved in cell survival and apoptosis [99]. Polyphenols are well characterized plant-derived antioxidants [80,100]. This is more complex, and the mechanisms of cellular activity are not well known. There is evidence of mild oxidative activity that results in a beneficial cellular response and may modulate signaling between mitochondria and endoplasmic reticulum relevant to cellular energy regulation and ROS generation [80]. Polyphenols further regulate eicosanoid production exerting anti-inflammatory activity. These compounds are therefore increasingly investigated with supporting benefit for inflammatory-mediated chronic disorders [100]. Flavonoids are able to react with and neutralize superoxide, lipid peroxide radicals, protecting cellular structures, and conversely may generate H2O2 with cytotoxic consequences [101]. As a flavonoid group, anthocyanins have anti-inflammatory and antioxidant activity, mediated in part through modulation of nuclear factor-kappa (NF-kβ) and mitogen-activated protein kinase signaling, regulating inflammatory gene transcription, and molecular activity [102].
JAK-STAT pathway: Testicular development, spermatogenesis and fertility
Rajender Singh in Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Ligand molecules are the extracellular molecules that cannot cross the membrane but through ligand-receptor interaction have the potential to activate an intracellular cell signaling cascade. Initially, the JAK-STAT pathway was discovered by interferon (IFN)-induced intracellular signaling. But later, a large number of cytokines, interferons and growth hormones were known to induce JAK-STAT signaling. In mammals, these ligand molecules are classified into various families depending on their structural and functional characteristics (10) (Table 15.3). In Drosophila, Upd is the only known ligand molecule for inducing JAK-STAT signaling. The unpaired gene encodes a 47 kDa secretory glycoprotein, localized to an extracellular matrix (ECM) (16). While curating a Drosophila database, other Upd-like genes have also been identified, such as Upd2 (19) and Upd3 (17).
Improving cellular uptake of therapeutic entities through interaction with components of cell membrane
Published in Drug Delivery, 2019
Renshuai Zhang, Xiaofei Qin, Fandong Kong, Pengwei Chen, Guojun Pan
Proteins are the second major components of cell membranes and some of them can mediate cellular uptake termed also receptor-mediated uptake in general describing. In order to profound the understanding of key role of trans-membrane proteins in mediated drug delivery, they were divided into two categories, transporters and receptors in this review. For instance, some trans-membrane proteins are transporters that carry small molecules (e.g. glucose) into the cell. Some other proteins are known as receptors to mediate the cell signaling pathway for growth and proliferation. For transporters, they maintained the normal metabolism of cells via transferring necessary nutrients from the outside to the inside. Meanwhile, some transporters showed high affinity to ligand-drug conjugates and even ligand-drug carrier complexes. Thus, it provided an ideal opportunity for enhancing drug delivery and improving drug targeting. For receptors, they can be especially bound by natural ligands or monoclonal antibodies (mAbs), and thus mediated cellular signal or used in the treatment of disease. To date, lots of mAbs have been conjugated to small molecule drugs or drug carriers for drug delivery. Additionally, some transporters can also be targeted by mAbs, such as folate receptors (FR) which transport folate into cells, and meanwhile as antigens can specially bind anti-FR antibody. Importantly, covalent attachment of small molecule drugs or drug carriers to antibodies did not significantly influence their cell internalization, thus providing another delivery strategy utilizing interaction between antibody and membrane proteins.
The application of gene silencing in proteomics: from laboratory to clinic
Published in Expert Review of Proteomics, 2018
Maura Brioschi, Cristina Banfi
The well-known relevance of protein–protein interactions in cell signaling has led to the development of several approaches to dissect them. Traditionally, interactions have been studied using the yeast two-hybrid system, which is based on the fusion of two proteins, a ‘bait’ and a ‘prey,’ with transcription activators that are able to activate the transcription of a reporter gene only when the two proteins interact one with each other. However, this method can give many false-positive and false-negative identifications, neglecting also the effects of subcellular localization or PTMs too, because it studies the interactions outside normal physiological conditions [82]. Alternatively, interaction partners could be identified using overexpressed proteins tagged to allow a specific purification of the target protein together with its interactors. However, also in this case, the properties of the protein of interest could be modified by the overexpression itself, which could also saturate the system and mask the dynamic changes of interactions in response to biological stimuli [83]. Thus, the method of choice is still the co-immunopurification of interactors with antibodies/resins against the protein of interest in a physiological context, even if issues on the specificity of the approach still exist.
Endometrium receptivity in premature ovarian insufficiency – how to improve fertility rate and predict diseases?
Published in Gynecological Endocrinology, 2018
Svetlana Vujović, Miomira Ivovic, Milina Tančić-Gajić, Ljiljana Marina, Aleksandar Ljubic, Svetlana Dragojević-Dikić, Andrea Ricardo Genazzani
Sexual steroids control the implantation process, a cascade of cytokines, growth factors, and adhesion molecules [21]. The progression of implantation and pregnancy require immunological tolerance which allows embryo survival. Hypoestrogenism in POI directly influences immune response. The large population of lympho-myeloid cells, found in endometrium, play variety of roles in the implantation process. Cell signaling pathways and specific proteins are involved in maturation, differentiation and functionality of the endometrium. Proteins expressed in luminal and glandular epithelia are: cadherins, beta-catenin, CD166/ALCAM, glycodelin A, leukemia inhibiting factor, stem cell factor and its receptor c-kit, epidermal growth factor (EGF), mucin 1, integrin alfaVbeta3, insulin like growth factor (IGF) etc.
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