Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGF beta signalling

Aims Telomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and upregulation of proapoptotic transcription factors. Pim1 is a cardioprotective kinase that antagonizes the aging phenotype of cardiomyocytes and delays cellular senescence by maintaining telomere length, but the mechanism remains unknown. Another pathway responsible for regulating tetomere length is the transforming growth factor beta (TGF beta) signalling pathway where inhibiting TGF beta signalling maintains telomere Length. The relationship between Pim1 and TGF beta has not been explored. This study delineates the mechanism of telomere length regulation by the interplay between Pim1 and components of TGF beta signalling pathways in proliferating A549 cells and post-mitotic cardiomyocytes.Methods and results Telomere length was maintained by lentiviral-mediated overexpression of PIM1 and inhibition of TGF beta signalling in re A549 cells. Telomere length maintenance was further demonstrated in isolated cardiomyocytes from mice with cardiac-specific overexpression of PIM1 and by pharmacological inhibition of TGF beta signalling. Mechanistically, Pim1 inhibited phosphorylation of Smad2, preventing its translocation into the nucleus and repressing expression of TGF beta pathway genes.Conclusion Pim1 maintains tetomere lengths in cardiomyocytes by inhibiting phosphorylation of the TGF beta pathway downstream effectors Smad2 and Smad3, which prevents repression of telomerase reverse transcriptase. Findings from this study demonstrate a novel mechanism of telomere length maintenance and provide a potential target for preserving cardiac function.[GRAPHICS].Therapeutic cell differentiatio

Integrated optimization of the adsorption of theaflavins from black tea on macroporous resins

In this work the adsorption and desorption parameters for the separation of theaflavins from tea are determined. The obtained data is used for a preliminary selection of the resin with the best adsorption capacity and desorption ratio. From the four tested resins the hydrophobic A-DVB resin has the best characteristics. In addition, the data was used to fit the adsorption isotherms at different temperatures to two theoretical models. The isotherms form the basis of a more extensive model that can be used to optimize the sorption separation yield. The selected resin will be used in a follow up study to determine the optimal operating conditions of the system, using design of experiments and analysis of variance