


Vol 10, No 4 (2016)
- Year: 2016
- Articles: 8
- URL: https://journals.rcsi.science/1990-7508/issue/view/12345
Article
Application of reporter strains for screening of new antibiotics
Abstract
Screening for new antibiotics remains an important area of biology and medicine. Elucidation of the antibiotic mechanism of action is an indispensable part for this type of research. Preferentially, it should be carried out quickly and cost-effectively, on the stage of primary screening. In this review we describe application of reporter strains for rapid classification of antibiotics by their mechanisms of action, without prior purification of active compounds and determination of their chemical structure.



The role of vascular endothelial growth factor in the regulation of development and functioning of the brain: New target molecules for pharmacotherapy
Abstract
There is evidence that members of the VEGF family are involved in the crucial processes in the brain: atherosclerosis, cerebral edema, neuroprotection, neurogenesis, angiogenesis, postischemic brain and vessel repair. Most of these effects are mediated by VEGF-A and the VEGFR-2 receptor. VEGF signaling pathways contain some potential targets relevant for pharmacological agents applicable for therapy of neurological diseases affecting the brain.



Apoptotic endonuclease EndoG induces alternative splicing of telomerase catalytic subunit hTERT and death of tumor cells
Abstract
Telomerase activity is known to be regulated by alternative splicing of its catalytic subunit hTERT (human Telomerase Reverse Transcriptase) mRNA. Induction of non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. Strong correlation was found between expression of EndoG and hTERT splice-variants in 12 colon cancer cell lines. Overexpression of EndoG in СаСо-2 cells downregulated the expression of active full-length hTERT variant and upregulated non-active spliced variant. Reduction of full-length hTERT caused downregulation of telomerase activity, dramatically shortening of telomeres length during cell divisions, converting cells to the replicative senescence state, activation of apoptosis and finally cell death. These data indicated the participation of EndoG in alternative splicing of mRNA of telomerase catalytic subunit, regulation of telomerase activity and cell fate.



The maternal effect in infantile autism: Elevated DNA damage degree in patients and their mothers
Abstract
Infantile autism is a common disorder of mental development; besides hereditary predisposition, various environmental factors, including the condition of the mother’s body during pregnancy (“maternal effect”), have a significant impact on its appearance. Oxidative stress is suggested to play a key role in the pathogenesis of infantile autism. It causes a prominent genotoxic effect, which is realized through appearance of single and double strand breaks of the nuclear DNA. In patients with infantile autism and their mothers we evaluated the degree of DNA damage by using the DNA comet assay and determining the comet tail moment and DNA percent ratio in the tail. These two parameters demonstrated strong correlation (r = 0.90). Mean and median values of both parameters were significantly higher in samples from autistic children, than in agematching healthy controls. Interestingly, these parameters were also higher in healthy mothers of autistic children and they did not differ from the values in the group of autistic children. In the control group of healthy women of reproductive age, who had no children with autism, the mean value of the DNA comet tail moment significantly differed from the group of mothers of autistic children, but not from the control group of healthy children. The results suggest that mentally healthy mothers of autistic children have some genotoxic factors, which can determine development of the pathological process in the fetus via the environmental “maternal effect” during gestation.



Regulation of ABCA1 and ABCG1 transporter gene expression in the intraabdominal adipose tissue
Abstract
Tissue specific expression of genes encoding the cholesterol transporters ABCA1 and ABCG1 as well as genes encoding the most important transcriptional regulators of adipogenesis (LXRα, LXRβ, PPARγ and RORα) has been investigated in intraabdominal adipose tissue (IAT) samples from obese patients and patients without overweight. A direct correlation between the content of ABCA1 and ABCG1 proteins and the RORα protein level (r = 0.480, p < 0.05; r = 0.435, p < 0.05, respectively) suggests involvement of the transcription factor RORα in the regulation of ABCA1 and ABCG1 protein levels in IAT. ABCA1 and ABCG1 gene expression positively correlated with such obesity indicators as body mass index (BMI) (r = 0.522, p = 0.004; r = 0.594, p = 0.001, respectively) and waist circumference (r = 0.403, p = 0.033; r = 0.474, p = 0.013, respectively). The development of obesity is also associated with decreased IAT levels of RORα and LXRβ mRNA (p = 0.016 and p = 0.002, respectively). This suggest that the nuclear factor RORα can play a significant role in the regulation of cholesterol metabolism and control IAT expression of ABCA1 and ABCG1 genes, while the level of IAT LXRβ gene expression may be an important factor associated with the development of obesity.



Activity of redox-regulatory systems in the tumor and surrounding tissues in various histological types of tumors
Abstract
According to modern concepts, a malignant tumor is a complex dynamic system possessing numerous links with both the immediate environment and remote non-malignant tissues and organs. Changes in their redox balance can result in disruption of the normal tissue control. The aim of our study was to compare activity of enzymes influencing the redox state in the tumor tissue, peritumoral area, and nonmalignant tissues (taken by resection line) at various histological tumor variants. We found similar close level of reduced glutathione in the tissues of gastric adenocarcinoma and vulvar squamous cell carcinoma; however, dynamics of this parameter in the tumor surrounding tissues was different. In contrast to gastric adenocarcinoma, vulvar squamous cell carcinoma was characterized by a significant increase in glutathione content in the tumor tissue and increased activity of all investigated enzymes of the glutathione system in the tumor tissue and its peritumoral area as compared with the surrounding non-malignant tissue. These results underlie existence of clear differences in the functioning of the redox regulatory systems in the tumor and surrounding tissues of various histological origin and localization; these differences may be possibly attributed to different mechanisms involved in maintenance of the redox balance in the originally non-malignant tissues.



Cytotoxic activity and molecular modeling of progestins, pregna-D′-pentaranes
Abstract
The cytotoxic activity of synthetic progestins (pregna-D′-pentaranes II–V), full agonists of the progesterone receptor (PR), has been investigated towards PR-positive and PR-negative cells of human breast carcinoma. These compounds were more active in PR-positive MCF-7 cells than in PR-negative MDA-MB-453 cells. The tested compounds did not demonstrate cytotoxic effects towards normal epithelial MDCK cells. Molecular modeling of studied steroids with PR showed that all progestins with close energy values could bind to the ligand binding domain (LBD) of PR and the magnitude of the energy exceeded the value estimated for the progesterone molecule. Thus, the studied progestins are active towards different molecular subtypes of breast cancer and represent a promising class of chemical compounds for oncology.



Antibodies against modified low-density lipoproteins and their complexes in blood of patients with various manifestations of atherosclerosis
Abstract
The study included 79 patients with coronary artery disease (CAD), 25 individuals with preclinical atherosclerosis and 59 healthy individuals. Key lipid parameters were examined in all the participants. Levels of antibodies (Abs) (IgG and IgM) against low density lipoproteins (LDL) modified by malondialdehyde (MDA), acetic anhydride and hypochlorite, were determined by the enzyme-linked immunosorbent assay (ELISA). Abs specificity was tested by competitive ELISA. Circulating immune complexes (CIC) were isolated by polyethylene glycol precipitation followed by determination of their cholesterol by the enzymatic method. Abs to hypochlorite-modified LDL (hypochlorite-LDL) detected in the serum samples did not demonstrate cross-reactivity with MDA-modified LDL (MDA-LDL) and acetylated LDL (acetyl-LDL). Patients with CAD had increased levels of CIC (p < 0.0001) and decreased levels of Abs (IgM) to hypochlorite- LDL, compared with healthy controls and patients with preclinical atherosclerosis (p = 0.006). A correlation between the levels of Abs (IgG) to the hypochlorite-LDL and Abs to MDA-LDL and acetyl-LDL was found. The content of the Abs (IgM) to MDA-LDL and acetyl-LDL correlated with CIC-cholesterol concentrations, while lipid parameters did not correlate with Abs levels.


