Activation of PKC results in improved contractile effects and Ca2+ cycling by inhibition of PP2A-B56α.

Protein phosphatase 2A (PP2A) represents a heterotrimer that is responsible for the dephosphorylation of important regulatory myocardial proteins. This study was aimed to test whether the phosphorylation of PP2A-B56α at Ser41 by PKC is involved in the regulation of myocyte Ca2+ cycling and contraction. For this purpose, heart preparations of wild-type (WT) and transgenic mice overexpressing the nonphosphorylatable S41A mutant form (TG) were stimulated by administration of the direct PKC activator phorbol 12-myristate 13-acetate (PMA), and functional effects were studied. PKC activation was accompanied by the inhibition of PP2A activity in WT cardiomyocytes, whereas this effect was absent in TG. Consistently, the increase in the sarcomere length shortening and the peak amplitude of Ca2+ transients after PMA administration in WT cardiomyocytes was attenuated in TG. However, the costimulation with 1 µM isoprenaline was able to offset these functional deficits. Moreover, TG hearts did not show an increase in the phosphorylation of the myosin-binding protein C after administration of PMA but was detected in corresponding WT. PMA modulated voltage-dependent activation of the L-type Ca2+ channel (LTCC) differently in the two genotypes, shifting V1/2a by +1.5 mV in TG and by -2.4 mV in WT. In the presence of PMA, ICaL inactivation remained unchanged in TG, whereas it was slower in corresponding WT. Our data suggest that PKC-activated enhancement of myocyte contraction and intracellular Ca2+ signaling is mediated by phosphorylation of B56α at Ser41, leading to a decrease in PP2A activity.NEW & NOTEWORTHY The importance of the serine-41 phosphorylation site on B56α in reducing PP2A activity was demonstrated for the first time using a transgenic mutation model. Direct activation of PKC inhibits PP2A, leading to increased phosphorylation of MyBP-C in cardiomyocytes. The increased phosphorylation of contractile proteins is influenced by the PKC-phosphoB56α-PP2A signaling cascade resulting in improved intracellular Ca2+ handling and enhanced contractility and relaxation. PKC-mediated inhibition of PP2A also leads to modulation of the LTCC activation and inactivation kinetics.

Learning from the Experiences in the COVID-19 Pandemic - Impact on Quality of Life and Challenges for the Staff of a Dermatological Hospital and Rehabilitation Center in Germany: A Retrospective Analysis.

Purpose: During the COVID-19 pandemic, infections could also be detected among the staff and patients of the dermatological hospital Bad Bentheim (Germany). This retrospective analysis aims to better understand the impact of the pandemic on health care workers. The results could help improve future pandemic plans and measures to protect health care workers. Patients and Methods: In 2020, the whole staff (460 participants) of the dermatological hospital Bad Bentheim had been offered the option to be tested with respect to the antibody status on SARS-CoV-2 (IgG, IgM). The data were collected by means of a blood sample and subsequent questionnaires (22 questions for employees with positive SARS-CoV-2 serology) regarding disease severity, symptoms, disease duration, chains of infection, psychological and physical burden. Both groups were divided by positive or negative serology and data analysis was performed using an independent t-test. Results: It was shown that a COVID-19 Infection clinically presented itself as a respiratory tract infection, differed significantly in severity and duration, but also the long-term consequences in employees with proven COVID-19 disease (n=14, 3.7%) from the employees with non-COVID-19 respiratory diseases (33.6% of the seronegative employees). In addition, there was a significant psychological impairment and burden of COVID-19-affected employees. Our study showed unique insights into infection chains, disease courses, disease severity, symptoms and a significant psychological impairment and burden of COVID-19-affected employees among the COVID-19 positive staff. Conclusion: Our study shows deep insights into infection chains, disease courses, disease severity and symptoms among the COVID-19 positive staff and led to change of behavior with the disease itself and among the health care professionals. This knowledge has the potential to positively influence the handling of similar future events.