scholarly journals Epac signaling protein ligands as tools for studying their biological activity and creating new original drugs

2020 ◽  
pp. 3-17
Author(s):  
G. V. Mokrov ◽  
T. D. Nikiforova ◽  
S. A. Kryzhanovskiy
Keyword(s):  
Biological Activity ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
The Body ◽  
Physiological Functions ◽  
Signaling Protein ◽  
Protein Ligands ◽  
Biological Target ◽  
Effective Drugs ◽  
Structure And Functions

The review discusses modern views about the structure and functions of Epac proteins (exchange proteins directly activated by cyclic adenosine monophosphate). The involvement of Epac proteins both in the regulation of the physiological functions of the body and in the initiation of various pathological processes allows to consider them as a fundamentally new biological target for creating original, highly effective drugs. Information on existing Epac protein agonists and antagonists was collected, and the influence of Epac ligands structure on the values of their affinity and selectivity was analyzed. Presumptive mechanisms of the interaction of ligands with Epac proteins are presented.

scholarly journals An injectable refrigerated hydrogel for Inducing local hypothermia and neuroprotection against traumatic brain injury

2020 ◽  
Author(s):  
yuhan Han ◽  
ZhengZhong Han ◽  
Xuyang Huang ◽  
Feng Qian ◽  
Jun Jia ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Side Effects ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Controlled Drug Release ◽  
The Body ◽  
Whole Body ◽  
Local Hypothermia ◽  
Whole Body Cooling

Abstract Hypothermia is a promising therapy for Traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI are not consistent in clinical studies due to several severe side effects. Here, an injectable refrigerated hydrogel is designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. The hydrogel has four advantages: (1) It can be injected into injured site after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) The hydrogel can biodegrade and be used for controlled drug release. (3) Released T1AM can bind to trace amine-associated receptor 1 (TAAR1) to produce cyclic adenosine monophosphate (cAMP), which induces hypothermia. (4) This hydrogel has an increased medical value due to its simple operation and ability to achieve timely treatment. This hydrogel is able to cool the brain to 30.25 ± 2.25 °C for 12 hours while maintaining the body temperature at 36.80 ± 1.75 °C after TBI. More importantly, the hypothermia induced by this hydrogel leads to the maintenance of blood-brain barrier (BBB) integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI. This cooling method can potentially be developed as a new approach for hypothermia treatment in TBI.

scholarly journals Protein Kinase Inhibitor Peptide as a Tool to Specifically Inhibit Protein Kinase A

2020 ◽  
Vol 11 ◽  
Author(s):  
Chong Liu ◽  
Ping Ke ◽  
Jingjing Zhang ◽  
Xiaoying Zhang ◽  
Xiongwen Chen
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Kinase Inhibitor ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Protein Kinase Inhibitor ◽  
The Body ◽  
Specific Method ◽  
Inhibitor Peptide ◽  
Kinase A

The protein kinase enzyme family plays a pivotal role in almost every aspect of cellular function, including cellular metabolism, division, proliferation, transcription, movement, and survival. Protein kinase A (PKA), whose activation is triggered by cyclic adenosine monophosphate (cAMP), is widely distributed in various systems and tissues throughout the body and highly related to pathogenesis and progression of various kinds of diseases. The inhibition of PKA activation is essential for the study of PKA functions. Protein kinase inhibitor peptide (PKI) is a potent, heat-stable, and specific PKA inhibitor. It has been demonstrated that PKI can block PKA-mediated phosphorylase activation. Since then, researchers have a lot of knowledge about PKI. PKI is considered to be the most effective and specific method to inhibit PKA and is widely used in related research. In this review, we will first introduce the knowledge on the activation of PKA and mechanisms related on the inhibitory effects of PKI on PKA. Then, we will compare PKI-mediated PKA inhibition vs. several popular methods of PKA inhibition.

scholarly journals Review on the Bioactivities of Quercetin

2020 ◽  
Vol 13 (3) ◽  
pp. 181-194
Author(s):  
Shabana ◽  
R. C. Jaysree ◽  
Rajendran . N
Keyword(s):  
Wide Spectrum ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Biological Response ◽  
Cyclic Adenosine Monophosphate ◽  
Black Tea ◽  
Adenosine Monophosphate ◽  
Mutant Gene ◽  
The Body ◽  
High Concentration

Quercetin, the most active bioflavonoid which is produced as a secondary metabolite by plants, is a polyphenol with a wide spectrum of bioactivities. This bioflavonoid is the ―nature‘s biological response modifier‖ as it interferes with the various allergens and other reactive compounds. Apple, oranges, tomatoes, onions, black tea and green tea are good sources of quercetin and it is also available commercially. After absorption in the small intestine and colon, quercetin conjugates with glucuronic acid and binds to albumin and passes to liver and benefits the body by its various bioactivities. Quercetin‘s antioxidant activity enhances the radical scavenging activity and metal chelation of the ions but the prooxidant activity depends on its high concentration. Further, quercetin interferes with the formation of leukotrienes from arachidonic acid showing its anti-inflammatory effect. A combined effect of quercetin and bromelain effectively suppresses the allergic reactions and the excessive inflammation resulting from bruising and tissue damage. The mutualistic effect of vitamin C and quercetin protects each other from getting oxidized. A direct relationship was also found to exist between quercetin's antiviral activity and enhancement of cyclic adenosine monophosphate (cAMP), which is a second messenger involved in many biological processes. Quercetin helps in down regulation of mutant gene p53 and inhibits the growth of cancerous cells by putting a check at G1 phase. This also controls the surpassing of the normal regulatory growth by the tumor cells and inhibits the production of heat shock proteins and thus showing its anticancer properties. Owing to the potential pharmaceutical properties of quercetin, the bioactivities, principle uses and mechanisms involved in the treatment of various diseases were reviewed in this paper. In addition, safety issues involved in the partake of quercetin by humans have also been discussed.

scholarly journals Role Of Triclosan (TCS)-Containing Hand Washes In Hormonal Imbalance And Impotency

2021 ◽  
Author(s):  
Abah Moses Owoicho ◽  
Mustapha Bakare ◽  
Deborah Oganya Ogenyi ◽  
Ogu Stephen ◽  
Ujah Moses Okwori
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
The Body ◽  
Hormone Levels ◽  
Hormonal Imbalance ◽  
Hypothermic Effect ◽  
The Central Nervous System ◽  
Low Levels ◽  
Trade Names

Research shows that, triclosan disrupts the biosynthesis of testosterone. when tested on isolated testicular leydig cells with various dosages, it was found out that triclosan dose-dependently decreases testosterone, and the mechanism is as follows: triclosan decreases the activity of adenylyl cyclase enzyme, resulting in the drop of cAMP (cyclic adenosine monophosphate). Another research shows that, triclosan completely hammered thyroid hormones, lowered luteinizing hormone levels, follicle stimulating hormone levels, and cholesterol synthesis. Concerns over triclosan interfering with the body‘s thyroid hor-mone metabolism led to a study that found that triclosan had a marked hypothermic effect, lowering the body temperature, and overall causing a ―nonspecific depressant effect on the central nervous system. Another study associated exposure to low levels (0.03 mi-crog/L) of triclosan with disrupted thyroid hormone. Due to the close resemblance of triclosan to certain estrogens, a more recent paper in Environment International shows that triclosan inhibits estrogen sulfotransferase in sheep placenta,an enzyme which helps metabolize the hormone and transport it to the developing fetus. The suspicion is that triclosan would be dangerous in pregnancy if enough of it gets through to the placenta to affect the enzyme. Conclusively, it is recommended that hands should be washed with detergent and warm water, or with bleach and complement with alcohol-containing hand sanitizers rather than using triclosan containing hand washes; also when selecting prod-ucts such as hand washes, antiseptic soaps, facial cleansers, toothpaste, deodorants, al-ways watch out for Triclosan trade names/chemical names on the ingredient list such as trichlorocarbonalide, irgasan®, Irgacare® and Microban®, triclosan is used as a built-in antimicrobial for product protection.

scholarly journals Secondary Metabolites of Plants as Modulators of Endothelium Functions

2021 ◽  
Vol 22 (5) ◽  
pp. 2533
Author(s):  
Anna Bartáková ◽  
Marie Nováková
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
The Body ◽  
Guanosine Monophosphate ◽  
Biologically Active ◽  
World Health ◽  
Intracellular Calcium Level ◽  
Health Organization ◽  
Active Substances

According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time—from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide–cyclic guanosine monophosphate activation, prostacyclin–cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.

scholarly journals Association of Salivary Content Alteration and Early Ageusia Symptoms in COVID-19 Infections: A Systematic Review

2020 ◽  
Vol 14 (S 01) ◽  
pp. S152-S158
Author(s):  
Tariq Abduljabbar ◽  
Rana S. Alhamdan ◽  
Modhi Al Deeb ◽  
Khulud A. AlAali ◽  
Fahim Vohra
Keyword(s):  
Salivary Glands ◽  
Viral Infections ◽  
Human Life ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Salivary Flow ◽  
Salivary Secretion ◽  
The Body ◽  
Guanosine Monophosphate ◽  
Asymptomatic Patients

AbstractCoronavirus disease 2019 (COVID 19) is a major threat to the health and prosperity of human life at present. It has resulted in loss of thousands of lives globally and has brought countries to the brink of economic, social, and health collapse. A major issue of this infection is the ease with which it transmits through salivary droplets and its survival for long durations outside the body. Therefore, its early detection is critical in prevention, diagnostic, and management efforts of COVID-19 patients. Loss of taste and smell is one of the early symptoms reported in these patients and the virus is abundantly found in the salivary secretion of the infected symptomatic and asymptomatic patients. Infection and inflammation of salivary glands are common among viral infections, particularly in the early stages, which lead to salivary composition changes. Chemosensory sensation of taste is critically dependent on the salivary flow rate and its inorganic constituents, protein levels, specific 3′,5′-cyclic adenosine monophosphate and 3′,5′-cyclic guanosine monophosphate levels, ghrelins, pH levels, and enzymes. Therefore, the question arises, “Does COVID-19 infection alter the salivary components and composition leading to early transient symptoms of Ageusia and hypogeusia?” This review shows association of the COVID-19 and Ageusia, in addition to the early viral infection of salivary glands and possible changes in salivary flow and content. Therefore, suggesting a potential association between early ageusia in COVID-19 infection and salivary compositional changes.

Mechanisms of ATP to cAMP Conversion Catalyzed by the Mammalian Adenylyl Cyclase: A Role of Magnesium Coordination Shells and Proton Wires

2019 ◽  
Author(s):  
Bella Grigorenko ◽  
Igor Polyakov ◽  
Alexander Nemukhin
Keyword(s):  
Adenylyl Cyclase ◽  
Bond Cleavage ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Md Simulations ◽  
Coordination Shell ◽  
Energy Profile ◽  
One Step ◽  
Type V

<p>We report a mechanism of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) conversion by the mammalian type V adenylyl cyclase revealed in molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) simulations. We characterize a set of computationally derived enzyme-substrate (ES) structures showing an important role of coordination shells of magnesium ions in the solvent accessible active site. Several stable six-fold coordination shells of Mg<sub>A</sub><sup>2+ </sup>are observed in MD simulations of ES complexes. In the lowest energy ES conformation, the coordination shell of Mg<sub>A</sub><sup>2+ </sup>does not include the O<sub>δ1</sub> atom of the conserved Asp440 residue. Starting from this conformation, a one-step reaction mechanism is characterized which includes proton transfer from the ribose O<sup>3'</sup>H<sup>3' </sup>group in ATP to Asp440 via a shuttling water molecule and P<sup>A</sup>-O<sup>3A</sup> bond cleavage and O<sup>3'</sup>-P<sup>A</sup> bond formation. The energy profile of this route is consistent with the observed reaction kinetics. In a higher energy ES conformation, Mg<sub>A</sub><sup>2+</sup> is bound to the O<sub>δ1</sub>(Asp440) atom as suggested in the relevant crystal structure of the protein with a substrate analog. The computed energy profile initiated by this ES is characterized by higher energy expenses to complete the reaction. Consistently with experimental data, we show that the Asp440Ala mutant of the enzyme should exhibit a reduced but retained activity. All considered reaction pathways include proton wires from the O<sup>3'</sup>H<sup>3' </sup>group via shuttling water molecules. </p>

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