We measure the time dependence of the ratio of decay rates for the rare decay D{0}-->K{+}pi{-} to the Cabibbo-favored decay D{0}-->K{-}pi;{+}. A signal of 12.7x10;{3} D{0}-->K{+}pi{-} decays was obtained using the Collider Detector at Fermilab II detector at the Fermilab Tevatron with an integrated luminosity of 1.5 fb;{-1}. We measure the D0-D[over ]{0} mixing parameters (R_{D},y{'},x{'2}), and find that the data are inconsistent with the no-mixing hypothesis with a probability equivalent to 3.8 Gaussian standard deviations.

Background and purpose: Diazoxide, a well-known opener of the mitochondrial ATP-sensitive potassium (mitoK ATP ) channel, has been demonstrated to exert cardioprotective effect against ischemic injury through the mitoK ATP channel and protein kinase C (PKC). We aimed to clarify the role of PKC isoforms and the relationship between the PKC isoforms and the mitoK ATP channel in diazoxide-induced cardioprotection. Experimental approach: In H9c2 cells and neonatal rat cardiomyocytes, PKC-e activation was examined by Western blotting and kinase assay. Flavoprotein fluorescence, mitochondrial Ca 2 þ and mitochondrial membrane potential were measured by confocal microscopy. Cell death was determined by TUNEL assay. Key results: Diazoxide (100 mM) induced translocation of PKC-e from the cytosolic to the mitochondrial fraction. Specific blockade of PKC-e by either eV1-2 or dominant negative mutant PKC-e (PKC-e KR) abolished the anti-apoptotic effect of diazoxide. Diazoxide-induced flavoprotein oxidation was inhibited by either eV1-2 or PKC-e KR transfection. Treatment with 5-hydroxydecanoate (5-HD) did not affect translocation and activation of PKC-e induced by diazoxide. Transfection with wild type PKC-e mimicked the flavoprotein-oxidizing effect of diazoxide, and this effect was completely blocked by eV1-2 or 5-HD. Diazoxide prevented the increase in mitochondrial Ca 2 þ , mitochondrial depolarization and cytochrome c release induced by hypoxia and all these effects of diazoxide were blocked by eV1-2 or 5-HD. Conclusions and Implications: Diazoxide induced isoform-specific translocation of PKC-e as an upstream signaling molecule for the mitoK ATP channel, rendering cardiomyocytes resistant to hypoxic injury through inhibition of the mitochondrial death pathway.