Regulation of Cytochrome b5 Expression by miR-223 in Human Liver: Effects on Cytochrome P450 Activities

Purpose: Cytochrome b 5 (b 5) is a hemoprotein that transfers electrons to several enzymes to fulfill functions in fatty acid desaturation, methemoglobin reduction, steroidogenesis, and drug metabolism. Despite the importance of b 5, the regulation of b 5 expression in human liver remains largely unknown. We investigated whether microRNA (miRNA) might be involved in the regulation of human b 5. Methods: Twenty-four human liver specimens were used for correlation analysis. In silico analysis and luciferase assay were performed to determine whether the predicted miRNAs functionally target to b 5. The miR-223 was overexpressed into HepG2 cells infected with adenovirus expressing human cytochrome P450. Results: In human livers, the b 5 protein levels were not positively correlated with the b 5 mRNA levels, and miR-223 levels were inversely correlated with the b 5 mRNA levels or the translational efficiencies. The luciferase assay showed that miR-223 functionally binds to the element in the 3′-untranslated region of b 5 mRNA. The overexpression of miR-223 significantly reduced the endogenous b 5 protein level and the mRNA stability in HepG2 cells. Moreover, the overexpression of miR-223 significantly reduced CYP3A4-catalyzed testosterone 6β-hydroxylation activity and CYP2E1-catalyzed chlorzoxazone 6-hydroxylase activity but not CYP1A2-catalyzed 7-ethoxyresorufin O-deethylase activity. Conclusions: miR-223 down-regulates b 5 expression in the human liver, modulating P450 activities. © 2013 Springer Science+Business Media New York

Utility of a Computed Tomography-Based Navigation System (O-Arm) for Partial Vertebrectomy for Lung Cancer Adjacent to the Thoracic Spine: Technical Case Report

We describe successful vertebrectomy from a posterior approach using a computed tomography (CT)-based navigation system (O-arm) in a 53-year-old man with adenocarcinoma of the posterior apex of the right lung with invasion of the adjacent rib, thoracic wall, and T2 and T3 vertebral bodies. En bloc partial vertebrectomy for lung cancer adjacent to the thoracic spine was planned using O-arm. First, laminectomy was performed from right T2 to T3, and pedicles and transverse processes of T2 to T3 were resected. O-arm was used to confirm the location of the cutting edge in the T2 to 3 right vertebral internal body, and osteotomy to the anterior cortex was performed with a chisel. Next, the patient was placed in a left decubitus position. The surgical specimen was extracted en bloc. This case shows that O-arm can be used reliably and easily in vertebrectomy from a posterior approach and can facilitate en bloc resection

Cigarette smoking substantially alters plasma microRNA profiles in healthy subjects

Circulating microRNAs (miRNAs) are receiving attention as potential biomarkers of various diseases, including cancers, chronic obstructive pulmonary disease, and cardiovascular disease. However, it is unknown whether the levels of circulating miRNAs in a healthy subject might vary with external factors in daily life. In this study, we investigated whether cigarette smoking, a habit that has spread throughout the world and is a risk factor for various diseases, affects plasma miRNA profiles. We determined the profiles of 11 smokers and 7 non-smokers by TaqMan MicroRNA array analysis. A larger number of miRNAs were detected in smokers than in non-smokers, and the plasma levels of two-thirds of the detected miRNAs (43 miRNAs) were significantly higher in smokers than in non-smokers. A principal component analysis of the plasma miRNA profiles clearly separated smokers and non-smokers. Twenty-four of the miRNAs were previously reported to be potential biomarkers of disease, suggesting the possibility that smoking status might interfere with the diagnosis of disease. Interestingly, we found that quitting smoking altered the plasma miRNA profiles to resemble those of non-smokers. These results suggested that the differences in the plasma miRNA profiles between smokers and non-smokers could be attributed to cigarette smoking. In addition, we found that an acute exposure of ex-smokers to cigarette smoke (smoking one cigarette) did not cause a dramatic change in the plasma miRNA profile. In conclusion, we found that repeated cigarette smoking substantially alters the plasma miRNA profile, interfering with the diagnosis of disease or signaling potential smoking-related diseases. © 2013 Elsevier Inc

14-3-3 proteins stabilize LGI1-ADAM22 levels to regulate seizure thresholds in mice

新たなてんかん治療戦略を提案 --脳の過剰興奮を阻止するタンパク質ADAM22の量が鍵--. 京都大学プレスリリース. 2021-12-15.What percentage of the protein function is required to prevent disease symptoms is a fundamental question in genetic disorders. Decreased transsynaptic LGI1-ADAM22 protein complexes, because of their mutations or autoantibodies, cause epilepsy and amnesia. However, it remains unclear how LGI1-ADAM22 levels are regulated and how much LGI1-ADAM22 function is required. Here, by genetic and structural analysis, we demonstrate that quantitative dual phosphorylation of ADAM22 by protein kinase A (PKA) mediates high-affinity binding of ADAM22 to dimerized 14-3-3. This interaction protects LGI1-ADAM22 from endocytosis-dependent degradation. Accordingly, forskolin-induced PKA activation increases ADAM22 levels. Leveraging a series of ADAM22 and LGI1 hypomorphic mice, we find that ∼50% of LGI1 and ∼10% of ADAM22 levels are sufficient to prevent lethal epilepsy. Furthermore, ADAM22 function is required in excitatory and inhibitory neurons. These results suggest strategies to increase LGI1-ADAM22 complexes over the required levels by targeting PKA or 14-3-3 for epilepsy treatment

Multi-layered model for rock-paper-scissors game: A swarm intelligence sustains biodiversity

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Morphological control of layered double hydroxide through a biomimetic approach using carboxylic and sulfonic acids

Layered double hydroxides (LDHs) have intercalation properties and are used in various applications. The performances of the LDH materials can be improved by controlling crystal morphology. Morphology of inorganic crystals is controlled by organic molecules in biomineralization. Inspired by biomineralization, we investigated the effect of the addition of mono, di and triacids as morphological control agents on crystal morphology of LDH synthesized by the homogeneous precipitation method. Morphology of LDH was changed from hexagonal plate to stacked disc by addition of monoacids, namely acetic acid and methanesulfonic acid, in the reaction solution. Flower-shaped LDH crystals were formed in the presence of diacids and a triacid, namely succinic acid, 1,2-ethanedisulfonic acid and 1,2,3-propanetricarboxylic acid. We found that the morphology of the LDH crystals was controlled by the number of functional group on the morphological control agent rather than the type of functional group. These findings can contribute for the development of novel and functional LDH materials with precisely controlled morphology

A study of archaeal enzymes involved in polar lipid synthesis linking amino acid sequence information, genomic contexts and lipid composition

Cellular membrane lipids, of which phospholipids are the major constituents, form one of the characteristic features that distinguish Archaea from other organisms. In this study, we focused on the steps in archaeal phospholipid synthetic pathways that generate polar lipids such as archaetidylserine, archaetidylglycerol, and archaetidylinositol. Only archaetidylserine synthase (ASS), from Methanothermobacter thermautotrophicus,has been experimentally identified. Other enzymes have not been fully examined. Through database searching, we detected many archaeal hypothetical proteins that show sequence similarity to members of the CDP alcohol phosphatidyltransferase family, such as phosphatidylserine synthase (PSS), phosphatidylglycerol synthase (PGS) and phosphatidylinositol synthase (PIS) derived from Bacteria and Eukarya. The archaeal hypothetical proteins were classified into two groups, based on the sequence similarity. Members of the first group, including ASS from M. thermautotrophicus, were closely related to PSS. The rough agreement between PSS homologue distribution within Archaea and the experimentally identified distribution of archaetidylserine suggested that the hypothetical proteins are ASSs. We found that an open reading frame (ORF) tends to be adjacent to that of ASS in the genome, and that the order of the two ORFs is conserved. The sequence similarity of phosphatidylserine decarboxylase to the product of the ORF next to the ASS gene, together with the genomic context conservation, suggests that the ORF encodes archaetidylserine decarboxylase, which may transform archaetidylserine to archaetidylethanolamine. The second group of archaeal hypothetical proteins was related to PGS and PIS. The members of this group were subjected to molecular phylogenetic analysis, together with PGSs and PISs and it was found that they formed two distinct clusters in the molecular phylogenetic tree. The distribution of members of each cluster within Archaea roughly corresponded to the experimentally identified distribution of archaetidylglycerol or archaetidylinositol. The molecular phylogenetic tree patterns and the correspondence to the membrane compositions suggest that the two clusters in this group correspond to archaetidylglycerol synthases and archaetidylinositol synthases. No archaeal hypothetical protein with sequence similarity to known phosphatidylcholine synthases was detected in this study