Expression analysis of Baf60c during heart regeneration in axolotls and neonatal mice.

Some organisms, such as zebrafish, urodele amphibians, and newborn mice, have a capacity for heart regeneration following injury. However, adult mammals fail to regenerate their hearts. To know why newborn mice can regenerate their hearts, we focused on epigenetic factors, which are involved in cell differentiation in many tissues. Baf60c (BRG1/BRM-associated factor 60c), a component of ATP-dependent chromatin-remodeling complexes, has an essential role for cardiomyocyte differentiation at the early heart development. To address the function of Baf60c in postnatal heart homeostasis and regeneration, we examined the detailed expression/localization patterns of Baf60c in both mice and axolotls. In the mouse heart development, Baf60c was highly expressed in the entire heart at the early stages, but gradually downregulated at the postnatal stages. During heart regeneration in neonatal mice and axolotls, Baf60c expression was strongly upregulated after resection. Interestingly, the timing of Baf60c upregulation after resection was consistent with the temporal dynamics of cardiomyocyte proliferation. Moreover, knockdown of Baf60c downregulated proliferation of neonatal mouse cardiomyocytes. These data suggested that Baf60c plays an important role in cardiomyocyte proliferation in heart development and regeneration. This is the first study indicating that Baf60c contributes to the heart regeneration in vertebrates.

BF3-Mediated cis-Selective Cycloaddition of O-Silyloxime with Alkenes.

A C-amide-substituted O-silylated oxime, (E)-(tert-butyldimethylsiloxyimino)acetic acid N,N-dimethylamide (8b), on treatment with 2.2 equiv of BF3·OEt2, in situ generated boracyclic nitrone-type intermediate BF3·14, which underwent cycloaddition with alkenes to give 3,5-cis-isoxazolidines as the major products. The mechanism was strongly supported by isolation of the reaction intermediate 14 that was characterized by X-ray diffraction and its further reaction. This cycloaddition was successfully applied to the synthesis of syn-HPA-12 known as an inhibitor of CERT that mediates the transport of ceramide.