Identification of protein kinase D as a novel contraction-activated kinase linked to GLUT4-mediated glucose uptake independent of AMPK

Contraction-induced glucose uptake is only partly mediated by AMPK activation. We examined whether the diacylglycerol-sensitive protein kinase D (PKD; also known as novel PKC isoform mu) is also involved in the regulation of glucose uptake in the contracting heart. As an experimental model, we used suspensions of cardiac myocytes, which were electrically stimulated to contract or treated with the contraction-mimicking agent oligomycin. Induction of contraction at 4 Hz in cardiac myocytes or treatment with 1 mu M oligomycin enhanced (i) autophosphorylation of PKD at Ser916 by 5.1- and 3.8-fold, respectively, (ii) phosphorylation of PKD's downstream target cardiac-troponin-I (cTnI) by 2.9- and 2.1-fold, respectively, and (iii) enzymatic activity of immunoprecipitated PKD towards the substrate peptide syntide-2 each by 1.5-fold. Although AMPK was also activated under these same conditions, in vitro phosphorylation assays and studies with cardiac myocytes from AMPK alpha 2(-/-) mice indicated that activation of PKD occurs independent of AMPK activation. CaMKK beta, and the cardiac-specific PKC isoforms alpha, beta, and epsilon were excluded as upstream kinases for PKD in contraction signaling because none of these kinases were activated by oligomycin. Stimulation of glucose uptake and induction of GLUT4 translocation in cardiac myocytes by contraction and oligomycin each were sensitive to inhibition by the PKC/PKD inhibitors staurosporin and calphostin-C. Together, these data elude to a role of PKD in contraction-induced GLUT4 translocation. Finally, the combined actions of PKD on cTnI phosphorylation and on GLUT4 translocation would efficiently link accelerated contraction mechanics to increased energy production when the heart is forced to increase its contractile activity

Quality of life and voice outcome of patients treated with transoral CO2 laser microsurgery for early glottic carcinoma (T1-T2): a 2-year follow-up study

Purpose Longitudinal studies in laryngeal cancer can provide clinicians information about short-term and long-term functional outcomes, like quality of life (QoL) and voice outco

Impact of Sn doping on the hydrogen detection characteristics of ZnO thin films: Insights from experimental and DFT combination

International audienceThe development of efficient chemical sensors based on semiconductor oxides is a major challenge. Low-cost equipment fabrication with a high sensor response towards H2 was the aim of our work. Chemical sensors were elaborated using zinc oxide, aluminum- and tin-doped zinc oxide. The samples were synthesized with a cost-effective chemical spray pyrolysis technique. Sn-doped ZnO response to hydrogen gas is the highest followed by ZnO and Al-doped ZnO, with a high sensitivity reaching 200 at 500 ppm, for 400 °C. DFT calculations revealed that O2 is strongly adsorbed on the ZnO-Al surface, resulting in the cancellation of the electrical conductance. Consequently, the approaching H2 gas will not possess sufficient energy to extract the strongly adsorbed oxygen from the surface, and no trapped electrons can be released back to the surface. In contrast, DFT calculations highlighted the potential of ZnO and Sn-doped ZnO to be used as hydrogen gas sensors. Charge transfer analysis revealed that only a small release of the trapped electrons occurs on the pure ZnO surface (0.14|e|), compared to Sn doped ZnO, in which a full release of free electrons was observed, resulting in a more favorable response to H2 and confirming the experimental results