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A Biophysical View on the Function and Activity of Endotoxins
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Ulrich Seydel, Andre Wiese, Andra B. Schromm, Klaus Brandenburg
As already pointed out, a prerequisite for normal cell functioning is the maintenance of a particular composition of the lipid matrix at given ambient conditions (17). Disturbances of this composition (e.g., by uptake of extraneous lipids) that differ in their chemical structure (e.g., acylation pattern, headgroup conformation, net electrical charge) from that of the normal constituents of the cell matrix, may lead to (1) alterations of membrane fluidity and/or permeability, (2) phase separation and domain formation,(3) disturbance of the lamellar membrane architecture, and (4) even internalization of the extraneous lipids. In many cases, the cell may be able to compensate for those changes by altering the composition of the lipid matrix by “homoviscous adaptation” (18). If this is not possible—certainly not on a time scale of minutes—any one of these membrane alterations may cause severe dysfunctions of the cell. Such dysfunctions may manifest themselves, for example, in transient or permanent alterations in the normal functioning of transmembrane proteins that might be involved in signal transduction. It would be predicted that membrane alterations and their influence on cell functioning would vary in severity in direct relationship to differences in the chemical structure of the constituents and the interacting lipids.
Signal Transduction Mechanisms Regulating Cytokine-Mediated Induction of Acute Phase Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Until recently, protein phosphatases were not considered to be key players in signal transduction cascades and were thought to be important only for reversing the effect of protein kinases. However, this viewpoint has changed and protein phosphatases are considered to play central and specific roles in cellular physiology.61-63 The role of protein phosphatases has been evaluated in the signal transduction mechanisms regulating the synthesis of acute phase proteins by IL-6 in the absence or presence of cytokines, and these studies have revealed that the serine protein phosphatase 1 and/or 2A may be important in regulating the induction of some of the acute phase proteins.49
The N-Formylpeptide Chemotactic Receptor
Published in Richard Horuk, Chemoattractant Ligands and Their Receptors, 2020
In addition to the work in COS cells reviewed in the previous section, frog oocytes may also provide an opportunity for further defining the signal transduction partners of FPR. In oocytes injected with cRNA for human FPR, mouse FPR, human FPRL1, or the human C5a receptor, ligand-induced calcium mobilization requires coinjection of a second natural RNA found in HL-60 and U937 cells, and probably many other cell types.35,44,96,97 Physical expression of FPR requires only injection of FPR cRNA.95 Thus, a complementary human factor is required to establish FPR signal transduction competency in the oocyte. Curiously, the factor is not required for functional expression of other types of G protein-coupled receptors, including chemokine receptors and the guinea pig platelet-activating factor receptor.98–101 This phenomenon may provide an opportunity to identify a novel element in the signal transduction pathways of the receptors that require it. cRNAs for mammalian Gαo, Gαil, Gα2, and Gαi3 do not complement human FPR.44 The mRNA for the factor is contained in a 3.5 kb size class of transcripts from HL-60 neutrophils.44,96 Cloning of the factor cDNA may be possible by complementation using an expression library made from this RNA.
Effects of MFG-E8 expression on the biological characteristics of ovarian cancer cells via the AKT/mTOR/S6K signalling pathway
Published in Journal of Obstetrics and Gynaecology, 2023
Na Li, Yazhuo Wang, Lin Liu, Pei Wang, Xiaohua Wu
Phosphorylated proteins are the main mediators of intracellular signal transduction. Phosphorylation not only activates proteins but also amplifies the transmitted signals and induces biological responses both inside and outside the cell. The AKT/mTOR/S6K signalling pathway, which is an important signal transduction pathway in cells, is involved in various aspects of cell growth, proliferation, and metabolic regulation. Abnormal functioning of this pathway can cause developmental defects and metabolic diseases, in addition to promoting tumour formation (Khan et al.2013, Li et al.2019). In another study, MFG-E8 was reported to be an important activator of the AKT pathway (Zhao et al.2017). Here, we found that MFG-E8 silencing in SKOV3 cells inhibited not only AKT phosphorylation but also the phosphorylation of mTOR and its downstream S6K, suggesting that MFG-E8 may participate in the biological functions of tumour cells by regulating the mTOR/S6K signalling pathway.
Second messengers and their importance for novel drug treatments of patients with bipolar disorder
Published in International Review of Psychiatry, 2022
Gabriele Sani, Georgios D. Kotzalidis, Federica Fiaschè, Giovanni Manfredi, S. Nassir Ghaemi
Cells interact with each other and with distant stimuli through receptors embedded in their cell membranes, so to preserve their inner integrity and their homeostasis. The receptor ligand-receptor interaction is then transduced in a message to the internal of the cell, which subsequently reacts, providing a response to the environment. What intervenes between the receptor ligand-(the first messenger)-receptor interaction and the response, be the receptor ligand a hormone or a neurotransmitter, is regulated through molecular chains that constitute cascades, termed second messenger cascades. Second (and third, fourth, and so on) messengers are intracellular signalling molecules which are activated within the cell in response to the extracellular-membrane receptor event. Second messengers, once activated, trigger cellular changes in cascades, termed intracellular signal transduction cascades, which regard proliferation, differentiation, migration, survival, apoptosis and, in the case of neurons, depolarization.
The effects and molecular mechanism of heat stress on spermatogenesis and the mitigation measures
Published in Systems Biology in Reproductive Medicine, 2022
Yuanyuan Gao, Chen Wang, Kaixian Wang, Chaofan He, Ke Hu, Meng Liang
The expression of genes in male germ cells also changes when they are exposed to external heat stress. However, whether the regulation of gene expression is directly caused by the heat stress response remains controversial. Nevertheless, it is indisputable that changes in gene expression inside spermatocytes lead to changes in the protein content or localization within cells. When spermatocytes are stimulated by heat, genes related to defense, regulation, and repair will be up-regulated, while other genes that affect the differentiation and development of germ cells and associated with meiosis may be down-regulated (Kim et al. 2013). When the heat stress response occurs in the testis, the expression of the gene encoding the heat shock protein 1 (HSP1) is up-regulated and the level of the HSP protein is increased. In addition, other up-regulated genes include those responsible for apoptosis, cell adhesion, and signal transduction. When DNA damage is too extensive to repair, p53, which is involved in cell cycle arrest and apoptosis promotion, is also up-regulated to detect and eliminate damaged cells (Absalan et al. 2012). Common genetic changes in cryptorchidism are shown in Table 1.