Cytochrome c/cardiolipin relations in mitochondria: a kiss of death

Recently, phospholipid peroxidation products gained a reputation as key regulatory molecules and participants in oxidative signaling pathways. During apoptosis, a mitochondria-specific phospholipid, cardiolipin (CL), interacts with cytochrome c (cyt c) to form a peroxidase complex that catalyzes CL oxidation; this process plays a pivotal role in the mitochondrial stage of the execution of the cell death program. This review is focused on redox mechanisms and essential structural features of cyt c’s conversion into a CL-specific peroxidase that represent an interesting and maybe still unique example of a functionally significant ligand change in hemoproteins. Furthermore, specific characteristics of CL in mitochondria—its asymmetric transmembrane distribution and mechanisms of collapse, the regulation of its synthesis, remodeling, and fatty acid composition—are given significant consideration. Finally, new concepts in drug discovery based on the design of mitochondria-targeted inhibitors of cyt c/CL peroxidase and CL peroxidation with antiapoptotic effects are presented.     

Distribution of fish in the complex of floodplain-riverbed biotopes of the Irtysh

Distribution, composition, and movements of fish within the floodplain-riverbed complex of the Lower Irtysh are investigated. The principal working tools were hydroacoustic computerized complexes for the detection of fish aggregations and of their movements in the floodplain water course. Twenty-four-hour hydroacoustic observations revealed the predominantly crepuscular-nocturnal type of activity of most fish and the mass downstream migration of juveniles at the onset of the night. Seasonal traits of formation of fish aggregations on key biotopes of the Irtysh are revealed, and their biological harmony is shown. The necessity that fish distribution should be analyzed as a dynamic phenomenon is shown.     

DNA methylation-associated colonic mucosal immune and defense responses in treatment-na?ve pediatric ulcerative colitis

Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn’s disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P < 0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD.     

Molecular complexes of ivy and licorice saponins with sildenafil citrate (Viagra) and their biological activity

The molecular complexation of triterpene glycosides α-hederin (hederagenin 3-O-α-L-rhamnopyranosyl-(l → 2)-O-α-L-arabinopyranoside), hederasaponin C (hederagenin 3-O-α-L-rhamnopyranosyl-(l → 2)-O-α-L-arabinopyranosyl-28-O-α-L-rhamnopyranosyl-(l → 4)-O-β-D-glucopyranosyl-(l → 6)-O-β-D-glucopyranoside), and glycyram (monoammonium glycyrrhizinate) with sildenafil citrate was investigated for the first time using electrospray ionization mass spectroscopy. The glycosides form a complex in a 1: 1 molar ratio. The influence of the complex on Avena sativa seeds germination and its ichthyotoxicity against Poecilia reticulata were studied.     

Oxidative stress following traumatic brain injury in rats: quantitation of biomarkers and detection of free radical intermediates

Oxidative stress may contribute to many pathophysiologic changes that occur after traumatic brain injury. In the current study, contemporary methods of detecting oxidative stress were used in a rodent model of traumatic brain injury. The level of the stable product derived from peroxidation of arachidonyl residues in phospholipids, 8-epi-prostaglandin F(2alpha), was increased at 6 and 24 h after traumatic brain injury. Furthermore, relative amounts of fluorescent end products of lipid peroxidation in brain extracts were increased at 6 and 24 h after trauma compared with sham-operated controls. The total antioxidant reserves of brain homogenates and water-soluble antioxidant reserves as well as tissue concentrations of ascorbate, GSH, and protein sulfhydryls were reduced after traumatic brain injury. A selective inhibitor of cyclooxygenase-2, SC 58125, prevented depletion of ascorbate and thiols, the two major water-soluble antioxidants in traumatized brain. Electron paramagnetic resonance (EPR) spectroscopy of rat cortex homogenates failed to detect any radical adducts with a spin trap, 5,5-dimethyl-1-pyrroline N:-oxide, but did detect ascorbate radical signals. The ascorbate radical EPR signals increased in brain homogenates derived from traumatized brain samples compared with sham-operated controls. These results along with detailed model experiments in vitro indicate that ascorbate is a major antioxidant in brain and that the EPR assay of ascorbate radicals may be used to monitor production of free radicals in brain tissue after traumatic brain injury.     

Effect of salinity on diazotrophic activity and microbial composition of phototrophic communities from Bitter-1 soda lake (Kulunda Steppe,Russia)

Bitter-1 is a shallow hypersaline soda lake in Kulunda Steppe (Altai region, Russia). During a study period between 2005 and 2016, the salinity in the littoral area of the lake fluctuated within the range from 85 to 400 g/L (in July of each year). Light-dependent nitrogen fixation occurred in this lake up to the salt-saturating conditions. The rates increased with a decrease in salinity, both under environmental conditions and in laboratory simulations. The salinities below 100 g/L were favorable for light-dependent nitrogen fixation, while the process was dramatically inhibited above 200 g/L salts. The analysis of nifH genes in environmental samples and in enrichment cultures of diazotrophic phototrophs suggested that anaerobic fermenting and sulfate-reducing bacteria could participate in the dark nitrogen fixation process up to soda-saturating conditions. However, we cannot exclude the possibility that haloalkaliphilic nonheterocystous cyanobacteria (Euhalothece sp. and Geitlerinema sp.) and anoxygenic purple sulfur bacteria (Ectothiorhodospira sp.) might also play a role in the process at light conditions. The heterocystous cyanobacterium Nodularia sp. develops at low salinity (below 80 g/L) that is not characteristic for Bitter-1 Lake and thus does not make a significant contribution to the nitrogen fixation in this lake.

     

Effect of chronic administration of ethanol on the blood-brain barrier permeability of 14C-tyrosine and horseradish peroxidase in rats

Chronic 10-days oral ethanol administration in doses 8-11 g/kg per day has been shown to increase blood-brain barrier penetration for peripherally administered 14C-tyrosine in Wistar heavy- and light-drinker rats. No changes in BBB permeability for horseradish peroxidase has been found. Chronic effect of ethanol on BBB systems of specific and unspecific transport in rats heavy- and light-drinkers is discussed.     

DNA barcodes effectively identify the morphologically similar Common Opossum (Didelphis marsupialis) and Virginia Opossum (Didelphis virginiana) from areas of sympatry in Mexico

Two morphologically similar species of opossum from the genus Didelphis-Didelphis virginiana and Didelphis marsupialis-cooccur sympatrically in Mexico. High intraspecific variation complicates their morphological discrimination, under both field and museum conditions. This study aims to evaluate the utility and reliability of using DNA barcodes (short standardized genome fragments used for DNA-based identification) to distinguish these two species. Sequences of the cytochrome c oxidase subunit I (Cox1) mitochondrial gene were obtained from 12 D. marsupialis and 29 D. virginiana individuals and were compared using the neighbor-joining (NJ) algorithm with Kimura's two-parameter (K2P) model of nucleotide substitution. Average K2P distances were 1.56% within D. virginiana and 1.65% in D. marsupialis. Interspecific distances between D. virginiana and D. marsupialis varied from 7.8 to 9.3% and their barcode sequences formed distinct non-overlapping clusters on NJ trees. All sympatric specimens of both species were effectively discriminated, confirming the utility of Cox1 barcoding as a tool for taxonomic identification of these morphologically similar taxa.     

Effect of pharmacological substances on the altered permeability of the hemato-encephalic barrier for 14C-tyrosine due to ethanol

It has been demonstrated that membrane-stabilizing agents, chlorpromazine and alpha-tocopherol, have no effect on the increased blood-brain barrier permeability for 14C-tyrosine, induced by a single injection of ethanol at a dose of 2 and 4 g/kg. Dopaminergic antagonist haloperidol prevented the increase of blood-brain barrier permeability induced by a single injection of 2 g/kg of ethanol and diminished the elevated barrier permeability caused by chronic 10-day alcoholization of animals, including abstinent ones. The role of membrane and neuromediator components in the mechanisms regulating blood-brain barrier functions is discussed.