Effects of repeated desflurane and sevoflurane anesthesia on enzymatic free radical scavanger system

Background: To investigate the possible effects of repeated sevoflurane and desflurane anesthesia on hepatocellular system by evaluating the free radical metabolism, hepatocellular enzymes and histopatholgical changes in rats. Methods: Four groups of animals were studied. Sevoflurane 2% (v/v) and desflurane 6% (v/v) in air/O₂ were administered to animals in group II (n = 9) and III (n = 9) respectively. 100% (v/v) O₂ was administered in group IV (n = 9). Administration was done for 60 minutes over 3 days. Nine animals were allocated to control group (group I), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GSH-Px), glutathione-s-transferase (GST) and thiobarbituric acid reactive substances (TBARS) were studied. Also electron microscopy was performed. Results: Catalase, SOD, GSH-Px, GST activities and TBARS levels were significantly higher in groups II and III than in group I (p < 0.05). All parameters were significantly higher in groups II versus group IV (p < 0.05). On the other hand, SOD, GSH-Px and GST activities were significantly elevated in group III than IV, but CAT activity and TBARS levels were not significantly. Catalase, SOD, GSH-Px, GST but not TBARS levels were significantly higher in groups II and III than in group IV (p < 0.05). TBARS levels were higher in group III than in group IV, but this elevation was not statistically significant. CAT, SOD and GSH-Px activities were significantly higher in groups II than in group III (p < 0.05). Conclusion: Although electron microscopy findings were similar for group II and III, we can conclude that sevoflurane might cause more cellular damage than desflurane by causing higher activation of free radical metabolising enzymes.     

Crystal structure of RS21-C6, involved in nucleoside triphosphate pyrophosphohydrolysis

RS21-C6, which is highly expressed in all vertebrate genomes and green plants, is proposed to have nucleoside triphosphate pyrophosphohydrolase activity. Here, we report the crystal structures of the core fragment of RS21-C6, named RSCUT, and the complex with the substrate 5-methyl dCTP. The refined structure of RSCUT consists mainly of alpha-helices and shows formation of a tightly associated tetramer. On the basis of the structure of the RSCUT-m5dCTP complex and the results of pyrophosphatase activity assays, several key residues involved in the substrate binding of RS21-C6 have been identified. Tetramer formation is shown to be required for substrate binding.     

Spinophilin inhibits the binding of RGS8 to M1-mAChR but enhances the regulatory function of RGS8

We showed previously that RGS8 directly binds to the third intracellular loop (i3L) of the M1 muscarinic acetylcholine receptor using the sequence MPRR at the N-terminus of RGS8 and specifically inhibits signal transduction. Here, we identified spinophilin (SPL) as an RGS8-interacting protein. We found that the SPL-binding site of RGS8 is the MPRR sequence, and the M1 receptor and SPL compete for binding to RGS8. However, we also observed that the expression of SPL significantly enhances the inhibitory function of RGS8, and that SPL can bind to the M1 receptor, demonstrating the indirect binding of RGS8 to the M1 receptor through SPL for an efficient regulatory function.     

Exploring the genomes: From Arabidopsis to crops

Model systems have played a crucial role for understanding biological processes at genetic, molecular and systems levels. Arabidopsis thaliana is one of the best studied model species for higher plants. Large genomic resources and mutant collections made Arabidopsis an excellent source for functional and comparative genomics. Rice and Brachypodium have a great potential to become model systems for grasses. Given the agronomic importance of grass crops, it is an attractive strategy to apply knowledge from Arabidopsis to grasses. Despite many efforts successful reports are sparse. Knowledge transfer should generally work best between orthologous genes that share functionality and a common ancestor. In higher plants, however, recent genome projects revealed an active and rapid evolution of genome structure, which challenges the concept of one-to-one orthologous mates between two species. In this study, we estimated on the example of protein families that are involved in redox related processes, the impact of gene expansions on the success rate for a knowledge transfer from Arabidopsis to the grass species rice, sorghum and Brachypodium. The sparse synteny between dicot and monocot plants due to frequent rearrangements, translocations and gene losses strongly impairs and reduces the number of orthologs detectable by positional conservation. To address the limitations of sparse synteny and expanded gene families, we applied for the detection of orthologs in this study orthoMCL, a sequence-based approach that allows to group closely related paralogs into one orthologous gene cluster. For a total of 49 out of 170 Arabidopsis genes we could identify conserved copy numbers between the dicot model and the grass annotations whereas approximately one third (34.7%, 59 genes) of the selected Arabidopsis genes lack an assignment to any of the grass genome annotations. The remaining 62 Arabidopsis genes represent groups that are considerably biased in their copy numbers between Arabidopsis and all or most of the three grass genomes.     

The glutathione-S-transferase gene polymorphisms (GSTM1 and GSTT1) and idiopathic male infertility risk: A meta-analysis

Published data on the association between male infertility and the glutathione-S-transferase (GST) gene polymorphism are inclusive. To drive a more precise estimation, we performed a meta-analysis based on 1897 cases and 1785 controls from 15 published case–control studies. PubMed and CBMdisc literature research were conducted to identify all eligible studies investigating such a relationship. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.