Proto-Oncogene and Onco-Suppressor Gene Expression
Enrique Pimentel in Handbook of Growth Factors, 2017
Growth factors and other extracellular signaling agents are involved in regulating the expression of cellular genes, including the expression of genes associated with the control mechanisms of cell differentiation and cell proliferation. The levels of expression of certain genes, called “immediate-early” genes or early-response genes, are rapidly altered by the exposure of sensitive cells to the signaling agents. Other genes may be regulated secondarily to the early cellular response and are considered as late-response genes. Frequently, the genes regulated by growth factors and other extracellular signaling molecules are proto-oncogenes or tumor suppressor genes whose products are localized mainly in the nucleus. The nuclear localization of these products may depend on the presence of specific amino acid sequences that are required for their interaction with the nuclear pore complex.12 The proto-oncogene products Myc, Myb, Fos, Jun, Ets, and Rel function as transcription factors and their expression may be regulated at the transcriptional and/or posttranscriptional level by extracellular signaling agents. The regulation may include reversible phosphorylation/dephosphorylation of the protein.13 The p53 and RB tumor suppressor proteins are localized mainly in the nucleus, and their functions are also regulated by phosphorylation at specific amino acid residues. All these proto-oncogene and tumor suppressor gene products have an important role in growth control.
Pesticides and Chronic Diseases
William J. Rea, Kalpana D. Patel in Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
On the other hand, early studies identified transcription factors as critical phosphoproteins in signaling cascades. Immediate early genes control gene expression and therefore affect long-term cellular responses. Abou-Donia et al.9 have demonstrated that the transcription of c-fos is elevated in OPIDN, perhaps through the activation of cAMP (adenosine monophosphate) response element binding (CREB) which is phosphorylated by CaM kinase II. Subsequent to c-fos activation,255 they observed altered gene expression of CaM kinase II,253 neurofilaments,256 glial fibrillary acidic protein (GFAP), and vimentin.257 Their results also showed an increase in medium (NF-M) and a decrease in low (NF-L) and high (NF-H) molecular weight neurofilaments in the spinal cords of hens treated with DFP.256 This imbalance in the stoichiometry of neurofilament proteins interferes with their interaction with microtubules and promotes neurofilament dissociation from microtubules, leading to the aggregation of both cytoskeletal proteins.258 Immunohistochemical studies in NS tissues from TOCP- and DFP-treated hens demonstrated aberrant aggregation of phosphorylated neurofilament, tubulin, and CaM kinase II.259 This process may occur in the OP-stimulated chemically sensitive patient where we see changes in the spinal cords of some long-standing chemically sensitive patients who are exposed to OP.
Cocaine Pharmacology and Drug Interaction in the Fetal-Maternal Unit
Richard J. Konkol, George D. Olsen in Prenatal Cocaine Exposure, 2020
Several recent papers suggest that the expression of immediate early genes (IEGs) is changed by acute and chronic cocaine exposure. IEGs are a class of genes which respond to environmental signals such as neurotransmitters and growth factors. The products of some of these genes go on to act as transcription factors for the late response genes.76 The IEGs may play a critical role in mediating stimulus-induced neuronal plasticity and have been implicated in behavioral tolerance and sensitization to cocaine.76 In this regard, cocaine is capable of causing a brief rise in mRNA of the effector IEG protein arc (activity-regulated, cytoskeleton-associated) in the striatum.77 This protein is associated with the actin cytoskeleton in the cell body and dendrites of striatal neurons. In another study using in-situ hybridization,78 the cellular phenotype in the striatum which showed increased c-fos activity after acute cocaine administration was neurons containing substance P, but not enkephalin. When IEG expression was studied in the withdrawal period, reductions of zif268 and c-fos were noted.79 This reduction lasted several hours after a single dose. If multiple cocaine doses were given, a reduction of these mRNAs was seen for several days, suggesting chronic cocaine exposure is capable of significantly lowering mRNA levels.
Preclinical stress research: where are we headed? An early career investigator’s perspective
Published in Stress, 2018
Anand Gururajan, Aron Kos, Juan Pablo Lopez
Recent developments in what is generally referred to as activity driven labeling of neuronal populations have opened up new avenues to dissect neural ensembles and mapping them in greater detail. More importantly, it has allowed researchers to access and manipulate these previously activated cell populations. A number of distinct labeling tools have been developed with varying properties in terms of specificity, signal to noise ratio and temporal activation. Central to most of the current available tools is the following observation that neural activity ultimately results in the expression of a number of immediate early genes (IEGs) (Guzowski, Setlow, Wagner, & McGaugh, 2001). By extracting promoter or enhancer sequences that drive the expression of IEGs and allowing them to control the expression of fluorescent reporters, opsins or other effector genes enables for permanent labeling of a previously transiently activated neuron. Some of the most widely used activity-dependent IEG promoter sequences are those of the Fos and Arc genes. An example of one of the possible applications of this technique was presented in a series of studies in which channelrhodopsin-2 expression was driven by c-fos activation (Liu et al., 2012; Ramirez et al., 2013; Redondo et al., 2014). Using this setup Ramirez et al. showed that optogenetic reactivation of a neural network associated with a positive experience within the hippocampus–amygdala–nucleus accumbens results in the suppression of depression-like behaviors induced by an acute stressor (Ramirez et al., 2015).
The Effect of Cytokine-Stimulation and Pharmacologic Intervention on PGE2 Production in Primary Human Conjunctival and Corneal Cells
Published in Ocular Immunology and Inflammation, 2020
Eisuke Shimizu, Hiroyuki Yazu, Yoshiyuki Satake, Kazumi Fukagawa, Naohiko Aketa, Dogru Murat, Naoko Okada, Hiroshi Fujishima
PG induces vasodilation, which is an important feature of local inflammation. We found that IL-4 and TNF-α stimulated PGE2 production by primary cultured corneal epithelium, keratocytes, conjunctival epithelium, and fibroblasts. Corneal and conjunctival epithelia were stimulated to a greater extent than keratocytes and fibroblasts from normal volunteers. Arachidonic acid, released from cell membrane phospholipids of activated cells, is metabolized to PG by the sequential activity of COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and displays characteristics of a “housekeeping” enzyme. COX-2 is the product of an immediate early gene that is rapidly induced and tightly regulated.15 COX-1 has well-defined physiological functions; its activation leads to the production of prostacyclin. When released by the endothelium COX-1 is anti-thrombogenic,
C-Fos mapping and EEG characteristics of multiple mice brain regions in pentylenetetrazol-induced seizure mice model
Published in Neurological Research, 2019
Huajun Yang, Wei Shan, Fei Zhu, Tingting Yu, Jingjing Fan, Anchen Guo, Fei Li, Xiaofeng Yang, Qun Wang
C-Fos is an immediate early gene (IEG) with activity-dependent protein expression. Expression of c-Fos is an indirect marker of neuronal activity, and as is often expressed when neurons generate the action potentials. It has been extensively used to map stimulus-induced neuronal activation [12,13]. Several studies have reported the expression of c-Fos in different brain regions during the evolution of seizures in PTZ-induced seizure models indicated multiple brain regions activity during seizure response. The subconvulsive dose of PTZ (10–40 mg/kg) induced c-Fos immunoreactivity in thalamus and hypothalamus regions of adult rats [2,14]. Repetitive intraperitoneal injections of subconvulsive doses of PTZ induced seizures including absence-like, clonic, tonic-clonic seizures and status epilepticus, and were accompanied by c-Fos expression in the hippocampal dentate gyrus, and cortex [4]. For temporal profile of c-Fos induction, seizures induced by PTZ led to increased c-Fos expression at immunohistochemical level in rodents at 30 min. Maximum expression levels were observed at 1 h and 2 h after seizure induction, returning to baseline level at 6 h [15]. A second seizure induced in rats was within the absolute or relative refractory period (1–3 h) after the first one, and triggered no change or a partial effect in c-Fos expression, suggesting some inhibitory mechanisms of neuronal activities after epileptic seizures [15].
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