Cellular Effects

Mitomycin C was found to have broad activity against a range of tumors and has been used clinically since the early 1960s [14, 15]. It causes many specific cellular effects, including inhibition of DNA synthesis, recombination, chromosome breakage, sister chromatid exchange, induction of DNA repair, and induction of... 

Fluorid ions stimulate bone formation by a direct mitogenic effect on osteoblasts mediated via protein kinase activation and other pathways. Further to these cellular effects, fluorides alter hydroxyapatite crystals in the bone matrix. In low doses, fluorides induce lamellar bone, while at higher doses abnormal woven bone with inferior quality is formed. The effect of fluorides on normal and abnormal (e.g. osteoporotic) bone therefore depends on the dose administered. 

Glucocorticoids. Figure 2 Cellular effect of glucocorticoids. Glucocorticoids can affect the activation of most resident and infiltrating cells with the airway suppressing either cell number or mediator release or both. In addition, glucocorticoids are able to decrease vascular permeablility (leak) within the airways that causes oedema and increase the expression of (32-receptors in smooth muscle cells. 

Another type of NR crosstalk, which has only recently been recognized, is the so-called nongenomic actions of several receptors that induce very rapid cellular effects. Effectively, evidence has accumulated over several decades that steroid receptors may have a role that does not require their transcriptional activation, such as modifying the activity of enzymes and ion channels. While the effects of steroids that are mediated by the modulation of gene expression do occur with a time lag of hours, steroids can induce an increase in several second messengers such as inositol triphosphate, cAMP, Ca2+, and the activation of MARK and PI3 kinase within seconds or minutes. Many mechanistic details of these nongenomic phenomena remain poorly understood. Notably, controversy still exists as to the identity of the receptors that initiate the non-genomic steroid actions. However, it now appears that at least some of the reported effects can be attributed to the same steroid receptors that are known as NRs. 

Peroxisome Proliferator-Activated Receptors. Table 1 PPARa target tissues, cellular effects, and physiological effects... 

Cellular Effects of Complement Activation. C5a is chemotactic for neutrophils, activates their oxidative metabolism, and induces secretion of lysosomal enzymes from the granulocytes and macrophages. C5a may also induce the production of cytokines and prostaglandins (H19, S14). 

Associating Cellular Effects with Target Enzyme Inhibition 133... 

ASSOCIATING CELLULAR EFFECTS WITH TARGET ENZYME INHIBITION... 

In an ideal situation a structural series of compounds will have unlimited cell permeability, and one can therefore expect a strict correlation between rank-order enzyme affinity (as measured by K, values) and the EC50 for cellular effects (the EC50 is the cellular or organismal equivalent of the in vitro IC50 i.e., the EC50 is the con-... 

Rosen JF. 1985. Metabolic and cellular effects of lead A guide to low-level lead toxicity in children. 

Adenosine exerts its cellular effects through G-protein-coupled cell membrane receptors, which are divided into classes Ai, A2a. A2B, and A3 (for reviews, see Fredholm, 1995 Haas Selbach, 2000 Dunwiddie Masino, 2001). Ai (A, R)... 

Mutagenesis studies have shown that morphine and sufentanil bind differently to the jj, receptor [83, 85]. Mutation of an aspartic acid at residue 114 of the // receptor to an asparagine resulted in a mutant that did not bind morphine and morphine was ineffective in inhibiting adenylyl cyclase via that receptor. In contrast, sufentanil bound to the mutant and wild-type receptors equally well and it effectively inhibited cAMP accumulation via the mutant receptor. These findings demonstrate that morphine and sufentanil have different requirements for binding to the // receptor. By binding differentially, these two agonists may induce the ft receptor to interact with different G proteins to induce distinct cellular effects. 

The DNA binding of trans-platinum complexes is thus quite rich and varied. The cellular effects of such adduct formation also appear to be significantly different from those of cisplatin. 

Schwartz JL, Baker V, Larios E and Chung FL. 2005. Molecular and cellular effects of green tea on oral cells of smokers a pilot study. Mol Nutr Food Res 49(1)43—51. 

A 65-year-old female receives digoxin and furosemide for GIF After several months, she develops nausea and vomiting. Serum K+ is 2.5 mFq/L. Electrocardiogram (EKG) reveals an AV conduction defect. What cellular effect is causing these new findings ... 

Investigations of the cellular effects of radiofrequency radiation provide evidence of damage to various types of avian and mammalian cells. These effects involve radiofrequency interactions with cell membranes, especially the plasma membrane. Effects include alterations in membrane cation transport, Na+/K+-ATPase activity, protein kinase activity, neutrophil precursor membrane receptors, firing rates and resting potentials of neurons, brain cell metabolism, DNA and RNA synthesis in glioma cells, and mitogenic effects on human lymphocytes (Cleary 1990). 

Cleary, S.F. 1990. Cellular effects of radiofrequency electromagnetic fields. Pages 339-356 in O.P. Ghandi (ed.). Biological Effects and Medical Applications of Electromagnetic Energy. Prentice Hall, Englewood Cliffs, NJ. 

Fibronectin is an extracellular matrix protein that mediates a variety of cellular effects. It is important in cell-cell and cell-substratum interactions ( 3.9), mediates reticuloendothelial cell activity and binds both to Clq (the first component of complement) and to bacteria. It also increases the tu-mouricidal activity of macrophages and activates complement receptors, by regulating the binding of C3b-coated particles to neutrophils. It may mediate attachment of Staphylococcus aureus to neutrophils and may also play a role as an adhesion factor, promoting the adhesion of neutrophils to surfaces. Fibronectin mRNA (8.7-8.8 kb) is detected only at low levels in... 

Examples of cellular effects by NO which are not related to cGMP include ... 

Opioids create their effects by acting at opioid receptors (table 8.3). These are, namely, p, k, and 5. Each is further divided into subtypes, which are differentially distributed throughout the nervous system pi, pi, 51, 52, k1, and k3. A k2 receptor was defined pharmacologically, but no one to date has cloned a receptor that resembles it (Zukin et al. 1998). Selective agonists have been developed for the receptor subtypes (see table 8.3). Naloxone is a general antagonist for all classical opioid receptors. All opioid receptors create cellular effects through G-protein-... 

A variety of studies demonstrate a central role for ASM and ceramide in several forms of apoptosis. Ceramide seems to regulate the activity of certain proteins and, thus, may function, in some circumstances, as a second messenger. In addition, the concept of raft modification hy ceramide provides a comprehensive model for cellular effects of ceramide, and perhaps a biophysical explanation for the diverse functions of this lipid. 

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