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Regulation of Airway Smooth Muscle Proliferation by β2-Adrenoceptor Agonists
Published in Alastair G. Stewart, AIRWAY WALL REMODELLING in ASTHMA, 2020
Alastair G. Stewart, Paul R. Tomlinson, Leslie Schachte
A number of genes contain sequences in the promoter regions called cAMP response elements (CREs) which are activated by CRE-binding protein (CREB). Increases in cAMP may cause activation and nuclear translocation of PKA, which is then able to phosphorylate CREB, increasing its transcriptional activity.147 CREB binds to a nuclear protein called CREB-binding protein (CBP)148 which is also bound by the phosphorylated (active) form of Jun. It has been suggested that limiting levels of CBP may cause competition between CREB and Jun, resulting in mutual inhibition.149 Given the importance of Jun in activating mitogen-sensitive genes (see Figure 4), it is plausible that cAMP could inhibit cell proliferation by phosphorylated CREB sequestering the available CBP and, therefore, inhibiting the transcriptional activity of Jun complexes.
Rubinstein−Taybi Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
It is clear that heterogeneous mutations in CBP/CREBBP domains and subsequent epigenetic alterations contribute to characteristic phenotypic features and cancer risk associated with RTS. In view of the fact that about 30% of RTS cases do not contain detectable mutations in either CREBBP or EP300, further studies are required to uncover other epigenetic mechanisms affecting histone acetylation and subsequently gene transcription that may potentially contribute to the development of RTS belonging to neither RTS1 nor RTS2.
The Emerging Role of Histone Deacetylase Inhibitors in the Treatment of Lymphoma
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
The involvement of the HATs and HDACs in cancer is well established. For example, mutations affecting HAT genes have been well described in colorectal and gastric cancers (2). The MYST family of HATs (MOZ) has been implicated in leukemogenesis, being found fused to a p300 homolog-CBP (a HAT) in acute myeloid leukemia (AML) (3). Mutations in CREB binding protein (CBP) leading to its loss of HAT activity have been found in the Rubinstein–Taybi syndrome (4), a disease characterized, among other things, by an increased incidence of neoplasia. In addition, numerous viruses target HATs: (i) adenovirus E1A oncoprotein, which binds to p300 through a domain required for viral transformation, likely contributes to its oncogenic potential (5); (ii) the HIV Tat protein, which interacts with TAF1 and p300/CBP altering chromatin condensation and presumably gene expression (6); and (iii) the EBNA2 protein of the Epstein–Barr virus, which is responsible for B-lymphocyte immortalization, binds to HDAC2 (7). These illustrative examples underscore the importance of these particular reactions and their effects on the transcriptional state of DNA. As such, these same reactions have now become the topic of intense focus, as new drugs, which appear to modulate this biology, become increasingly more available.
Polydrug Use and Co-occurring Substance Use Disorders in a Respondent Driven Sampling of Cocaine Base Paste Users in Santiago, Chile
Published in Journal of Psychoactive Drugs, 2022
Carla F. Olivari, Jorge Gaete, Nicolás Rodriguez, Esteban Pizarro, Paloma Del Villar, Esteban Calvo, Alvaro Castillo-Carniglia
In Latin America, the most widely available and used psychoactive drugs (after alcohol) are cannabis, cocaine hydrochloride and cocaine base paste (CBP). The latter, however, is the substance recognized as producing the most harm among users and is one of the main drugs of use among treatment patients at admission (Hynes et al. 2019; James et al., 2018). CBP is an intermediate product in the production of cocaine hydrochloride with a high addictive potential (Moraes et al. 2010). It is obtained by treating a solution of coca leaves and water with kerosene or diesel, and then adding sulfuric acid and an alkaline substance (i.e., potassium permanganate) to precipitate the cocaine base paste. CBP contains varying percentages of cocaine, and due to its volatility at high temperatures, and in regard to consumption, it is most commonly inhaled after its combustion in pipes or in cigarettes in combination with tobacco or cannabis (Moraes et al. 2010; Pascale et al. 2014).
Safety considerations with new antibacterial approaches for chronic bacterial prostatitis
Published in Expert Opinion on Drug Safety, 2022
Gianpaolo Perletti, Alberto Trinchieri, Konstantinos Stamatiou, Vittorio Magri
2 – Reports describing therapy for CBP with some of the drugs reviewed in this article are scant in some cases. Whereas antibiotics like aminoglycosides and macrolides are recommended by international guidelines (e.g. the European Association of Urology Guidelines [22]), the evidence concerning other antibacterial agents is often anecdotal and restricted to case reports or small case series. Thus, readers should be warned of the limited published evidence concerning some of the drugs listed above. This also shows that the management of chronic prostatitis is a challenging task for clinicians, and antibiotic selection must be adapted as much as possible to current recommendations. Adequately powered comparative studies, preferably in a randomized setting, are urgently needed. In our opinion, priority should be given to studies focusing on CBP caused (i) by Gram-positive pathogens, whose prevalence is increasing in some geographic areas, and (ii) by multidrug-resistant/carbapenemase-producing Enterobacteriaceae. Unfortunately, the antibiotic pipeline is drying out due to the lack of interest of multinational pharmaceutical companies. Spontaneous research triggered by scientific interest and in the interest of patients will therefore be highly meritorious.
Role of oxidative stress in pathophysiology of rheumatoid arthritis: insights into NRF2-KEAP1 signalling
Published in Autoimmunity, 2021
Gurjasmine Kaur, Aman Sharma, Archana Bhatnagar
Apart from Keap1-mediated ubiquitination, multilayered regulation of Nrf2 is characterized by various modifications, interactions, and epigenetic modulations affecting Nrf2 signalling cascade via (i) Nrf2 and Keap1 interactions by kinase system ERK/c-Jun N-terminal kinase (JNK), p38, MAPK/ERK (ii) Nrf2 localization by Protein Kinase C (PKC), Casein kinase 2 (CK2), GSK3β (iii) Nrf2 protein degradation via GSK3β/β-TrCP (iv) Nrf2-DNA binding (300/CBP, Maf) [44]. Brahma-related gene 1, an ATP-dependent chromatin remodeller reportedly enhances Nrf2-mediated transcription by interacting with Neh4 and Neh5. Acetylation by p300/CBP promotes binding of Nrf2 to ARE, whereas de-acetylation attenuates interaction causing transcriptional termination. Also, various protein partners i.e. p21, p62, caveolin-1 have been identified for amplifying the activation of Nrf2 whereas transcription factor BACH protein competes with Nrf2 for dimerization to sMaf [44,45].