scholarly journals In Vitro Investigation of Binding Interactions between Albumin–Gliclazide Model and Typical Hypotensive Drugs

2021 ◽  
Vol 23 (1) ◽  
pp. 286
Author(s):  
Ewa Zurawska-Plaksej ◽  
Rafal Wiglusz ◽  
Agnieszka Piwowar ◽  
Katarzyna Wiglusz
Keyword(s):  
Diabetes Management ◽  
Spectroscopic Techniques ◽  
Binding Interactions ◽  
Hypotensive Drugs ◽  
In Vitro Investigation ◽  
Model Protein ◽  
Albumin Molecule

Type 2 diabetes management usually requires polytherapy, which increases the risk of drug-to-drug interactions. Among the multiple diabetes comorbidities, hypertension is the most prevalent. This study aimed to investigate the binding interactions between the model protein, bovine albumin, and the hypoglycemic agent gliclazide (GLICL) in the presence of typical hypotensive drugs: quinapril hydrochloride (QUI), valsartan (VAL), furosemide (FUR), amlodipine besylate (AML), and atenolol (ATN). Spectroscopic techniques (fluorescence quenching, circular dichroism) and thermodynamic experiments were employed. The binding of the gliclazide to the albumin molecule was affected by the presence of an additional drug ligand, which was reflected by the reduced binding constant of the BSA–DRUG–GLICL system. This may indicate a possible GLICL displacement and its enhanced pharmacological effect, as manifested in clinical practice. The analysis of the thermodynamic parameters indicated the spontaneity of the reaction and emphasized the role of hydrogen bonding and van der Waals forces in these interactions. The secondary structure of the BSA remained almost unaffected.

Binding interactions of halogenated bisphenol A with mouse PPARα: In vitro investigation and molecular dynamics simulation

2018 ◽  
Vol 283 ◽  
pp. 32-38 ◽  
Author(s):  
Jie Zhang ◽  
Tiezhu Li ◽  
Tuoyi Wang ◽  
Tianzhu Guan ◽  
Hansong Yu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Bisphenol A ◽  
Dynamics Simulation ◽  
Binding Interactions ◽  
In Vitro Investigation

Role of specific probiotics in skin diseases: new insights from in vitro investigation

2021 ◽  
Author(s):  
Diletta Squarzanti ◽  
Paola Zanetta ◽  
Marcello Manfredi ◽  
Margherita Ormelli ◽  
Angela Amoruso ◽  
...  
Keyword(s):  
Skin Diseases ◽  
In Vitro Investigation

Cortisol-mediated potentiation of uterine artery contractility: effect of pregnancy

2002 ◽  
Vol 283 (1) ◽  
pp. H238-H246 ◽  
Author(s):  
Daliao Xiao ◽  
Xiaohui Huang ◽  
Soochan Bae ◽  
Charles A. Ducsay ◽  
Lubo Zhang
Keyword(s):  
Uterine Artery ◽  
Vascular Reactivity ◽  
Maternal Plasma ◽  
Apparent Dissociation Constant ◽  
Protein Levels ◽  
No Release ◽  
Endothelial Nitric Oxide

During pregnancy, maternal plasma cortisol concentrations approximately double. Given that cortisol plays an important role in the regulation of vascular reactivity, the present study investigated the potential role of cortisol in potentiation of uterine artery (UA) contractility and tested the hypothesis that pregnancy downregulated the cortisol-mediated potentiation. In vitro cortisol treatment (3, 10, or 30 ng/ml for 24 h) produced a dose-dependent increase in norepinephrine (NE)-induced contractions in both nonpregnant and pregnant (138–143 days gestation) sheep UA. However, this cortisol-mediated response was significantly attenuated by ∼50% in pregnant UA. The 11β-hydroxysteroid dehydrogenase (11-βHSD) inhibitor carbenoxolone did not change the effect of cortisol in nonpregnant UA but abolished its effect in pregnant UA by increasing the NE pD2 in control tissues from 6.20 ± 0.05 to 6.59 ± 0.11. The apparent dissociation constant value of NE α1-adrenoceptors was not changed by cortisol in pregnant UA but was decreased in nonpregnant UA. There was no difference in glucocorticoid receptor density between nonpregnant and pregnant UA. Cortisol significantly decreased endothelial nitric oxide (NO) synthase protein levels and NO release in both nonpregnant and pregnant UA, but the effect of cortisol was attenuated in pregnant UA by ∼50%. Carbenoxolone alone had no effects on NO release in nonpregnant UA but was decreased in pregnant UA. These results suggest that cortisol potentiates NE-mediated contractions by decreasing NO release and increasing NE-binding affinity to α1-adrenoceptors in nonpregnant UA. Pregnancy attenuates UA sensitivity to cortisol, which may be mediated by increasing type-2 11-βHSD activity in UA.

scholarly journals Bax signaling regulates palmitate-mediated apoptosis in C2C12 myotubes

2008 ◽  
Vol 295 (6) ◽  
pp. E1307-E1314 ◽  
Author(s):  
Jonathan M. Peterson ◽  
Yan Wang ◽  
Randall W. Bryner ◽  
David L. Williamson ◽  
Stephen E. Alway
Keyword(s):  
Insulin Resistance ◽  
Fold Increase ◽  
C2c12 Myotubes ◽  
Serum Starvation ◽  
Signaling Proteins ◽  
Induced Apoptosis ◽  
Apoptotic Effects

Insulin resistance is a primary characteristic of type 2 diabetes. Several lines of evidence suggest that accumulation of free fatty acids in skeletal muscle may at least in part contribute to insulin resistance and may be linked to mitochondrial dysfunction, leading to apoptosis. Palmitate treatment of several cell lines in vitro results in apoptosis and inhibits protein kinase B (Akt) activity in response to insulin. However, the role of Bax and Bcl-2 in regulating palmitate-induced apoptosis has not been well studied. Therefore, the purpose of this study was to determine whether palmitate-induced apoptosis in C2C12 myotubes is dependent on Bax to Bcl-2 binding. An additional purpose of this study was to determine whether the changes in Bax to Bcl-2 binding corresponded to decreases in Akt signaling in palmitate-treated myoblasts. Apoptotic signaling proteins were examined in C2C12 myotubes treated overnight with palmitate. Bax to Bcl-2 binding was determined through a coimmunoprecipitation assay that was performed in myotubes after 2 h of serum starvation, followed by 10 min of serum reintroduction. This experiment evaluated whether temporal Akt activity coincided with Bax to Bcl-2 binding. Last, the contribution of Bax to palmitate-induced apoptosis was determined by treatment with Bax siRNA. Palmitate treatment increased apoptosis in C2C12 myotubes as shown by a twofold increase in DNA fragmentation, an approximately fivefold increase in caspase-3 activity, and a 2.5-fold increase in caspase-9 activity. Palmitate treatment significantly reduced Akt protein expression and Akt activity. In addition, there was a fourfold reduction in Bax to Bcl-2 binding with palmitate treatment, which mirrored the reduction in AktSer473 phosphorylation. Furthermore, treatment of the C2C12 myotubes with Bax siRNA attenuated the apoptotic effects of palmitate treatment. These data show that palmitate induces Bax-mediated apoptosis in C2C12 myotubes and that this effect corresponds to reductions in AktSer473 phosphorylation.

scholarly journals PPARδActivity in Cardiovascular Diseases: A Potential Pharmacological Target

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Angela Tesse ◽  
Ramaroson Andriantsitohaina ◽  
Thierry Ragot
Keyword(s):  
Metabolic Diseases ◽  
Peroxisome Proliferator ◽  
In Vivo Models ◽  
Pharmacological Target ◽  
Cardiovascular Cells ◽  
Peroxisome Proliferator Activated Receptors

Activation of peroxisome proliferator-activated receptors (PPARs), and particularly of PPARαand PPARγ, using selective agonists, is currently used in the treatment of metabolic diseases such as hypertriglyceridemia and type 2 diabetes mellitus. PPARαand PPARγanti-inflammatory, antiproliferative and antiangiogenic properties in cardiovascular cells were extensively clarified in a variety of in vitro and in vivo models. In contrast, the role of PPARδin cardiovascular system is poorly understood. Prostacyclin, the predominant prostanoid released by vascular cells, is a putative endogenous agonist for PPARδ, but only recently PPARδselective synthetic agonists were found, improving studies about the physiological and pathophysiological roles of PPARδactivation. Recent reports suggest that the PPARδactivation may play a pivotal role to regulate inflammation, apoptosis, and cell proliferation, suggesting that this transcriptional factor could become an interesting pharmacological target to regulate cardiovascular cell apoptosis, proliferation, inflammation, and metabolism.

scholarly journals The role of macrophage polarization on fibroblast behavior-an in vitro investigation on titanium surfaces

2017 ◽  
Vol 22 (2) ◽  
pp. 847-857 ◽  
Author(s):  
Xuzhu Wang ◽  
Yulan Wang ◽  
Dieter D. Bosshardt ◽  
Richard J. Miron ◽  
Yufeng Zhang
Keyword(s):  
Macrophage Polarization ◽  
In Vitro Investigation ◽  
Titanium Surfaces

Porcine sst1 can physically interact with other somatostatin receptors, and its expression is regulated by metabolic/inflammatory sensors

2014 ◽  
Vol 306 (5) ◽  
pp. E483-E493 ◽  
Author(s):  
Manuel D. Gahete ◽  
Mario Durán-Prado ◽  
Elena Delgado-Niebla ◽  
Juan J. Garrido ◽  
Simon J. Rhodes ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Somatostatin Receptors ◽  
Amino Terminal ◽  
Mediated Effects ◽  
Relevant Role ◽  
Amino Terminal Domain ◽  
G Protein Coupled

The majority of the biological actions attributed to somatostatin (SST) are thought to be mediated by SST receptor 2 (sst2), the most ubiquitous sst, and, to a lesser extent, by sst5. However, a growing body of evidence suggests a relevant role of sst1 in mediating SST actions in (patho)physiological situations (i.e., endometriosis, type 2 diabetes). Moreover, sst1 together with sst2 and sst5 is involved in the well-known actions of SST on pituitary somatotropes in pig and primates. Here, we cloned the porcine sst1 (psst1) and performed a structural and functional characterization using both primary and heterologous models. The psst1 sequence presents the majority of signature motifs shared among G protein-coupled receptors and, specifically, among ssts and exhibits a high homology with other mammalian sst1, with only minor differences in the amino-terminal domain, reinforcing the idea of an early evolutive divergence between mammalian and nonmammalian sst1s. psst1 is functional in terms of decreasing cAMP levels in response to SST when transfected in heterologous models. The psst1 receptor is expressed in several tissues, and analyses of gene cis elements predict regulation by multiple transcription factors and metabolic stimuli. Finally, psst1 is coexpressed with other sst subtypes in various tissues, and in vitro data demonstrate that psst1 can interact with itself forming homodimers and with other ssts forming heterodimers. These data highlight the functional importance of sst1 on the SST-mediated effects and its functional interaction with different ssts, which point out the necessity of exploring the consequences of such interactions.

scholarly journals The role of glycemic self-control in diabetes management: based on the American Diabetes Association guidelines (2021)

2021 ◽  
pp. 286-292
Author(s):  
G. E. Runova
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
American Diabetes Association ◽  
Diabetes Management ◽  
Glucose Monitoring ◽  
Self Monitoring ◽  
Diabetes Technology

Glycemic control represents an integral part of diabetes mellitus (DM) therapy. It is not surprising that diabetes technology is evolving to not only create new routes of insulin administration, but also to improve the measurement of glycemia. A significant number of new glucose monitoring systems have been launched to the market over the past 10 years. Nevertheless, only 30% of patients with type 1 diabetes and very few patients with type 2 diabetes use continuous or flash glucose monitoring. The reason for this is not only the cost and technical difficulties of continuous glucose monitoring, but also its clinical appropriateness. There is indisputable evidence that patients who receive intensified insulin therapy, especially those with type 1 diabetes, need frequent self-monitoring / continuous glucose monitoring. As for patients with type 2 diabetes receiving basal insulin and / or other antihyperglycemic therapy, the data received seem to be contradictory and uncertain. However, most of the recommendations simmer down to the need for self-monitoring of blood glucose levels in patients with type 2 diabetes. The diabetes technology section of the American Diabetes Association guidelines 2021 goes into details about the role of self-monitoring of blood glucose in diabetes management, including the need for continuous patient education on the principles and rules of self-monitoring, interpretation and practical use of the results of self-monitoring, various standards of glucometers, factors affecting the accuracy of the results. 

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