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Diabetic cardiomyopathy is a secondary complication of diabetes with an unclear etiology. Based on a functional genomic evaluation of obesity-associated cardiac gene expression, we previously identified and cloned the gene encoding apolipoprotein O (APOO), which is overexpressed in hearts from diabetic patients. Here, we generated APOO-Tg mice, transgenic mouse lines that expresses physiological levels of human APOO in heart tissue. APOO-Tg mice fed a high-fat diet exhibited depressed ventricular function with reduced fractional shortening and ejection fraction, and myocardial sections from APOO-Tg mice revealed mitochondrial degenerative changes. In vivo fluorescent labeling and subcellular fractionation revealed that APOO localizes with mitochondria. Furthermore, APOO enhanced mitochondrial uncoupling and respiration, both of which were reduced by deletion of the N-terminus and by targeted knockdown of APOO. Consequently, fatty acid metabolism and ROS production were enhanced, leading to increased AMPK phosphorylation and Ppara and Pgcla expression. Finally, we demonstrated that the APOO-induced cascade of events generates a mitochondrial metabolic sink whereby accumulation of lipotoxic byproducts leads to lipoapoptosis, loss of cardiac cells, and cardiomyopathy, mimicking the diabetic heart-associated metabolic phenotypes. Our data suggest that APOO represents a link between impaired mitochondrial function and cardiomyopathy onset, and targeting APOO-dependent metabolic remodeling has potential as a strategy to adjust heart metabolism and protect the myocardium from impaired contractility., Introduction Increased susceptibility to cardiac injury in obesity and diabetes is evident in both human and animal studies (1-4). Cardiovascular complications are the leading cause of diabetes-related morbidity and mortality. [...]

The synthesis of esters by alkoxycarbonylation of aryl, heteroaryl and vinyl halides is presented. The reaction proceeds under atmospheric pressure of CO in the presence of a catalytic amount of CoCRACO. Sun lamp illumination was sufficient to catalyze the reaction, thus, eliminating the need for Co2(CO)8 and excess CH3I. The results showed that reaction follows a S(sub RN)1 pathway.

A method of fitting a base to a particular reaction has been evolved from an empirical study of the reactivity of several unimetal super bases and the synthetic effects of such base associations. Super base implies that the properties of various bases are combined to produce a basic reagent. A base refers to any nucleophile that can abstract a proton from an organic substate.

A study conveniently developed polycyclic cyclopentane derivatives by using methylenecyclobutanols 1 as starting materials, which were derived from the 1,2-cycladiene condensation of ketone enolates. Several polycyclic cyclopentan- or cyclopentenones were synthesized as a result of the transposition and transposition-elimination of triol derivatives 3,5 and 6. This study was based on the knowledge that nucleophilic complex bases capable of producing 1, 2-cycladienes from the respective 1-chlorocycloalkenes, were obtained from the ketone enolate stimulation of NaNH2.

NMR spectroscopic studies of the complex base of NaNH2-t-BuONa (2/1) reveal the presence of two new 23Na species. The complexity of the spectrum of this base, as compared with spectra of individual t-BuONa and NaNH2, confirms the presence of these species, which account for 80% of the spectrum. A comparison of the quadrupolar parameters of the 23Na species and pure t-BuONa and NaNH2 indicates variations in crystal structures.