A Biophysical View on the Function and Activity of Endotoxins
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
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.
Disorders of Growth and Differentiation
Jeremy R. Jass in Understanding Pathology, 2020
Cell division must be coordinated with the needs of tissue and indeed the entire organism. This is achieved by means of hormones and growth factors, hormone and growth factor receptors arranged upon the cell membrane, signal transduction pathways (transferring messages from cell membrane to nucleus) and nuclear proteins (to prepare the cell for division). The function of signal transduction pathways is to bring about amplification and integration of the various messages received by the array of receptors upon the cell surface and so relay an unambiguous message to the nucleus. These cascade systems operate through the enzymatic conversion of an inactive precursor to an active enzyme. This is achieved by a surprisingly limited number of mechanisms (Fig. 18). Some of the genes coding for growth factors, receptors, cell signalling molecules or nuclear proteins that drive mitogenesis are called proto-oncogenes. This is because mutated versions (oncogenes; see Chapter 23) have been shown to drive cell proliferation in neoplasms (Table 4).
Application of Phytodrug Delivery in Anticancer Therapy
Madhu Gupta, Durgesh Nandini Chauhan, Vikas Sharma, Nagendra Singh Chauhan in Novel Drug Delivery Systems for Phytoconstituents, 2020
Over the years, the anticancer mechanisms of many phytodrugs have been elucidated, including influencing the immune system, inflammatory response, cell growth, and cell apoptosis; details are summarized in Figure 9.1. Progress in molecular biology promoted the development of mechanism-based receptor screens to probe interactions among large molecules and find small molecules from natural products as potential drug candidates in cancer chemotherapy. For instance, the relationship between DNA repair, cancer, and DNA damage response (DDR) has been explored in detail for better cancer therapy (Jeggo et al., 2016). Besides, study on the alteration of signal transduction pathways during the occurrence of various types of tumors is of great significance and value, which can not only deepen our understanding of the mechanism of cancer, but also provide potential molecular targets for better development of anticancer drugs. Here we take NF-κB as an example, which can regulate cancer cell process through targeting one or more steps in the pathway (Chu, 2013, Hoesel and Schmid, 2013, Lan et al., 2012, Natoli, 2012). Carcinogens activate NF-κB, while anticancer therapeutics suppress NF-κB. The schematic description of the progression of tumor cell development and thus the molecular targets of different anticancer phytodrugs during tumor progression are presented in Figure 9.2.
Gαs and Gαq/11 protein coupling bias of two AVPR2 mutants (R68W and V162A) that cause nephrogenic diabetes insipidus
Published in Journal of Receptors and Signal Transduction, 2022
Beril Erdem Tuncdemir
G protein coupled receptors (GPCR) are involved in many physiological functions through G-protein signaling. They govern signal transduction of hormones, metabolites, neurotransmitters, odorant molecules, and ions via their specific topology which consists of transmembrane, extra-, and intracellular domains. Since approximately 800 members of GPCRs are identified in the human genome, they are the largest superfamily of cell receptors [1]. GPCRs are capable of transmitting a variety of extracellular signals into the cell and then they make a response through the second messengers. Ligand binding to the GPCR triggers a conformational change of the receptor and activates the dissociation of G-protein subunits (α subunit dissociates from βγ subunits) which activates downstream mediators to transduce the signal [2]. There are four subtypes of the alpha subunit of G-protein, including Gαs, Gαi/o, Gαq/11, and Gα12/13 which are responsible for generating different responses via second messengers [2]. For example, while Gαs (which is a stimulatory Gα protein) activation causes the generation of cAMP and subsequent activation of protein kinase A (PKA), Gαi/o (which is an inhibitory Gα protein) activation inhibits cAMP production and PKA activity in the cell. Also, signaling through Gαq/11 activates phospholipase C-β (PLCβ) which in turn induces inositol 1,4,5-triphosphate (IP3) and Ca2+ mobilization [3].
There and back again: a dendrimer’s tale
Published in Drug and Chemical Toxicology, 2022
Barbara Ziemba, Maciej Borowiec, Ida Franiak-Pietryga
The signal transduction pathway is a cascade of biochemical reactions involving the transmission of molecular signals from a cell exterior to its interior. Signals received by cells must be transmitted effectively to the target molecules to assure an appropriate response. Signaling pathway dysregulation can influence cell growth, proliferation, division, metabolism, or survival and lead to disease development. Dendrimers, as nanoparticles, may easily disrupt signal transduction by affecting any element of the pathway. Such activity may have adverse effects, but also advantages, e.g., in cancer or metabolic diseases therapy. Therefore, findings on dendrimers’ biological effects in terms of their interactions with key cellular signal transduction pathways may have important clinical implications.
Determination of cytokine profile and associated genes of the signaling pathway in HNSCC
Published in Journal of Receptors and Signal Transduction, 2022
Aysel Kalayci Yigin, Ali Azzawri, Kayhan Ozturk, Tulin Cora, Mehmet Seven
Signal transduction pathways play a vital role in the control of cellular communication, those from the extracellular environment, cytokines, chemokines, immune modulators, growth factors or hormones. Dysregulation of signaling pathways is one of the most frequent events in the malignant transformation of many cancers including HNSCC [14]. Secretion of polypeptides including cytokines, chemokines, growth factors or hormones and also other chemical inducers from the stromal and cancer cells activate a variety of signaling pathways for instance EGFR, phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinases (MAPKs) and mammalian target of rapamycin (mTOR). Most of the previous studies were mainly focused on a signal pathway and targeting only cancer cells [15,16]. HNSCCs have a high rate of genetic heterogeneity. For this reason, the identification of both the cytokines and growth factors that trigger signal transduction pathways and their associated signal pathways in tumor/adjacent normal tissues and cell lines will be important in determining the molecular pathogenesis of HNSCCs. In this study, we first performed a cytokine array and investigated genes in the associated signal pathway in tumor vs normal tissues of HNSCC.
Related Knowledge Centers
- Biochemical Cascade
- Cell Growth
- Cell Signaling
- Protein Kinase
- Protein Phosphorylation
- Metabolism
- Receptor
- Transcription
- Translation
- Post-Translational Modification