Sirt3 modulates fatty acid oxidation and attenuates cisplatin‐induced AKI in mice

Fatty acid oxidation (FAO) dysfunction is one of the important mechanisms of renal fibrosis. Sirtuin 3 (Sirt3) has been confirmed to alleviate acute kidney injury (AKI) by improving mitochondrial function and participate in the regulation of FAO in other disease models. However, it is not clear whether Sirt3 is involved in regulating FAO to improve the prognosis of AKI induced by cisplatin. Here, using a murine model of cisplatin‐induced AKI, we revealed that there were significantly FAO dysfunction and extensive lipid deposition in the mice with AKI. Metabolomics analysis suggested reprogrammed energy metabolism and decreased ATP production. In addition, fatty acid deposition can increase reactive oxygen species (ROS) production and induce apoptosis. Our data suggested that Sirt3 deletion aggravated FAO dysfunction, resulting in increased apoptosis of kidney tissues and aggravated renal injury. The activation of Sirt3 by honokiol could improve FAO and renal function and reduced fatty acid deposition in wide‐type mice, but not Sirt3‐defective mice. We concluded that Sirt3 may regulate FAO by deacetylating liver kinase B1 and activating AMP‐activated protein kinase. Also, the activation of Sirt3 by honokiol increased ATP production as well as reduced ROS and lipid peroxidation through improving mitochondrial function. Collectively, these results provide new evidence that Sirt3 is protective against AKI. Enhancing Sirt3 to improve FAO may be a potential strategy to prevent kidney injury in the future.     

Selectively Etching Vanadium Oxide to Modulate Surface Vacancies of Unary Metal–Based Electrocatalysts for High‐Performance Water Oxidation

Electrocatalytic water splitting for hydrogen generation is hindered by the sluggish kinetics of water oxidation, and highly efficient electrocatalysts for the oxygen evolution reaction (OER) are urgently required. Numerous bi‐ and multimetal‐based, low‐cost, high‐performance OER electrocatalysts have been developed. However, unary metal–based high‐performance electrocatalysts are seldom reported. In the present study, Co₂(OH)₃Cl/vanadium oxide (VO_y) composites are synthesized, from which VO_y is completely etched out by a simple cyclic voltammetry treatment, which simultaneously transforms Co₂(OH)₃Cl in situ to ultrafine CoOOH. The selective removal of VO_y modulates the nature of the surface in the obtained CoOOH by creating surface oxygen vacancies (V_o), along with disordered grain boundaries. The best‐performing CoOOH with optimum V_o is found to be associated with a low overpotential of 282 mV at 10 mA cm^?2 catalytic current density on a simple glassy carbon electrode for OER. This facile protocol of selectively etching VO_y to modulate the nature of the surface is successfully applied to synthesize another Fe‐based electrocatalyst with high OER performance, thus establishing its utility for unary metal–based electrocatalyst synthesis.     

Recent Progress in Electrocatalysts for Acidic Water Oxidation

Hydrogen is a clean and renewable energy carrier for powering future transportation and other applications. Water electrolysis is a promising option for hydrogen production from renewable resources such as wind and solar energy. To date, tremendous efforts have been devoted to the development of electrocatalysts and membranes for water electrolysis technology. In principle, water electrolysis in acidic media has several advantages over that in alkaline media, including favorable reaction kinetics, easy product separation, and low operating pressure. However, acidic water electrolysis poses higher requirements for the catalysts, especially the ones for the oxygen evolution reaction. It is a grand challenge to develop highly active, durable, and cost‐effective catalysts to replace precious metal catalysts for acidic water oxidation. In this article, an overview is presented of the latest developments in design and synthesis of electrocatalysts for acidic water oxidation, emphasizing new strategies for achieving high electrocatalytic activity while maintaining excellent durability at low cost. In particular, the reaction pathways and intermediates are discussed in detail to gain deeper insight into the oxygen evolution reaction mechanism, which is vital to rational design of more efficient electrocatalysts. Further, the remaining scientific challenges and possible strategies to overcome them are outlined, together with perspectives for future‐generation electrocatalysts that exploit nanoscale materials for water electrolysis.     

Assessment of chemical modifications of sites in the CDRs of recombinant antibodies

Modifications like asparagine deamidation, aspartate isomerization, methionine oxidation, and lysine glycation are typical degradations for recombinant antibodies. For the identification and functional evaluation of antibody critical quality attributes (CQAs) derived from chemical modifications in the complementary-determining regions (CDRs) and the conserved regions, an approach employing specific stress conditions, elevated temperatures, pH, oxidizing agents, and forced glycation with glucose incubation, was applied. The application of the specific stress conditions combined with ion exchange chromatography, proteolytic peptide mapping, quantitative liquid chromatography mass spectrometry, and functional evaluation by surface plasmon resonance analysis was adequate to identify and functionally assess chemical modification sites in the CDRs of a recombinant IgG1. LC-Met-4, LC-Asn-30/31, LC-Asn-92, HC-Met-100c, and HC Lys-33 were identified as potential CQAs. However, none of the assessed degradation products led to a complete loss of functionality if only one light or heavy chain of the native antibody was affected.     

Genome sequence of the Litoreibacter arenae type strain (DSM 19593T), a member of the Roseobacter clade isolated from sea sand

Litoreibacter arenae Kim et al. 2012 is a member of the genomically well-characterized Rhodobacteraceae clade within the Roseobacter clade. Representatives of this clade are known to be metabolically versatile and involved in marine carbon-producing and biogeochemical processes. They form a physiologically heterogeneous group of Alphaproteobacteria and were mostly found in coastal or polar waters, especially in symbiosis with algae, in microbial mats, in sediments or together with invertebrates and vertebrates. Here we describe the features of L. arenae DSM 19593^T, including novel aspects of its phenotype, together with the draft genome sequence and annotation. The 3,690,113 bp long genome consists of 17 scaffolds with 3,601 protein-coding and 56 RNA genes. This genome was sequenced as part of the activities of the Transregional Collaborative Research Centre 51 funded by the German Research Foundation (DFG).     

Spot14/Mig12 heterocomplex sequesters polymerization and restrains catalytic function of human acetyl‐CoA carboxylase 2

Acetyl‐CoA carboxylase 2 (ACC2) is an isoform of ACC functioning as a negative regulator of fatty acid β‐oxidation. Spot14, a thyroid hormone responsive protein, and Mig12, a Spot14 paralog, have recently been identified as regulators of fatty acid synthesis targeting ACC1, a distinctive subtype of ACC. Here, we examined whether Spot14/Mig12 modulates ACC2. Nanoscale protein topography mapped putative protein–protein interactions between purified human Spot14/Mig12 and ACC2, validated by functional assays. Human ACC2 displayed consistent enzymatic activity, and homogeneous particle distribution was probed by atomic force microscopy. Citrate‐induced polymerization and enzymatic activity of ACC2 were restrained by the addition of the recombinant Spot14/Mig12 heterocomplex but only partially by the oligo‐heterocomplex, demonstrating that the heterocomplex is a designated metabolic inhibitor of human ACC2. Moreover, Spot14/Mig12 demonstrated a sequestering role preventing an initial ACC2 nucleation step during filamentous polymer formation. Thus, the Spot14/Mig12 heterocomplex controls human ACC2 polymerization and catalytic function, emerging as a previously unrecognized molecular regulator in catalytic lipid metabolism. © 2013 The Authors. Journal of Molecular Recognition published by John Wiley & Sons, Ltd.     

Distribution of heavy metals in a sewage oxidation pond and their adsorption in residual solid (sewage sludge ash)

Abstract

Electrometric studies were carried out on the interaction of heavy metal ions such as manganese, chromium, nickel, copper, zinc, cadmium and lead with the extracted organic matter, humic and fulvic acid from the sludge in a sewage oxidation pond. The distribution of heavy metals was between 60 and 97%, which is associated with the solid waste (sludge) of the oxidation pond. The adsorption/removal efficiency of metal ions onto the sludge ash was more than 90% and 97%, respectively, in the pure system. To obtain the ash, the sludge was burnt at 500°C, treated with nitric acid (1+1) to leach out all the metals and then filtered; the residue left on the filter paper was the pure ash. Both this and that coated with organic matter were studied. The adsorption isotherm for metals, humic/fulvic acids and metal-humic/fulvic acid complexes in the metal-free sludge ash and in the organic matter in the pure system were studied using the Freundlich relationship. Good agreement was found suggesting that sediment and humic/fulvic acids have an important role in the mobility, dispersion and sedimentation of metal ions in an aquatic environment. More of these heavy metals are removed in the pure system than in the natural system. This may be due to the lesser availability of humic and fulvic acids in the lagoons during the short detention time of sewage in suspension in the oxidation pond, whereas the sludge which has settled to the bottom of the pond for several years contains rich decomposed organic matter in the form of humic and fulvic acids containing heavy metals. Such pure systems could be useful for the effective removal of heavy metals.     

A Crystalline Aminopeptidase from Streptomyces peptidofaciens: Physico-chemical Properties and Characteristics as a Ca-Metalloprotease

A crystalline aminopeptidase obtained from the culture filtrate of Streptomyces peptidofaciens KY 2389 appeared to be homogeneous on ultracentrifugation and acrylamide gel electrophoresis. The sedimentation coefficient, s_{20, w}., was determined to be 2.6 S. The molecular weight was estimated to be approximately 19,000 by sedimentation equilibrium studies. The amino acid analyses indicated that the enzyme was composed of 147 amino acid residues and contained no sulfhydryl group. The isoelectric point was found to be around pH 7.4 by isoelectric focusing on ampholites.

The enzyme required Ca²⁺ for its maximal activity and was strongly inhibited by some metal-chelating agents such as ethylenediaminetetraacetic acid (EDTA) and o-phenanthroline. The EDTA-inactivated enzyme restored its activity almost completely by the addition of Ca²⁺ The crystalline preparation of aminopeptidase contained 1 g-atom of calcium and about 2 g-atoms of magnesium per mole of enzyme protein, and the calcium was essential for the activity of the enzyme.     

A Model System for Convenient Fluorescent Labeling of Sugar Chain in Taka-amylase A

A convenient detection of sugar chains in Taka-amylase A (TAA) was done by using 40 μg of enzyme, where a decrease in the UV absorption of NaIO₄ during the periodate oxidation reaction was monitored. The periodate-oxidized sugar chain was labeled with a fluorescent reagent, N-1-ethylenediaminonaphthalene (EDAN), by incubation at pH 9.5 and 30°C for 1 h. The excess EDAN was removed by either quenching with o-phthaladehyde or Bio-Gel P-2 gel adsorption. Among the peptide fragments prepared from the EDAN-labeled TAA, a fluorescent peptide corresponding to the sugar chain was distinguished by the ODS column. These results suggest that periodate oxidation and subsequent fluorescent labeling were useful for the sensitive analysis of various glycoprotein samples.     

Inhibitory Effect of a Cirsium setidens Extract on Hepatic Fat Accumulation in Mice Fed a High-Fat Diet via the Induction of Fatty Acid β-Oxidation

Cirsium setidens is a perennial medicinal herb that is rich in flavonoids. We investigated in this study the effect of a C. setidens ethanol extract (CSE) on the development of nonalcoholic fatty liver in mice fed a high-fat diet (HF). C57BL/6J mice were fed either a control diet (CON) or HF for 8 weeks, and then fed CON, HF, or HF with 100 mg/kg of BW CSE (HF+CSE) for an additional 7 weeks. The final body weight and adipose tissue weight of the mice in the HF+CSE group were significantly lower than those in the HF group. CSE also markedly diminished both the lipid droplets in the liver tissues and decreased the hepatic and serum triglycerides (TG) concentrations. CSE strongly increased the hepatic mRNA levels of carnitine palmitoyltransferase (CPT1) and medium-chain acyl-CoA dehydrogenase (MCAD), the fatty acid β-oxidation enzymes. The hepatic levels of phosphorylated-AMP-activated protein kinase (AMPK) were significantly higher in the HF+CSF group than in the HF group. These results suggest that CSE inhibited hepatic fat accumulation by up-regulating the expression of the fatty acid β-oxidation genes.