Myocardial reperfusion injury is partially mediated by postis

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This study has confirmed that establishing a targeted LAMP, based on close co-operation between intensive care physicians and infectious disease specialists together with a restricted prescribing authority, can reduce the use of antibiotics.

Prolonged Ca2؉ stimulations often result in a decrease in contractile force of isolated, demembranated human ventricular cardiomyocytes, whereas intact cells are likely to be protected from this deterioration. We hypothesized that cytosolic protein kinase C (PKC) contributes to this protection. Prolonged contracture (10 min) of demembranated human cardiomyocytes at half-maximal Ca 2؉ resulted in a 37 ؎ 5% reduction of active force (p < 0.01), whereas no decrease (2 ؎ 3% increase) was observed in the presence of the cytosol (reconstituted myocytes). The PKC inhibitors GF 109203X and Gö 6976 (10 mol/liter) partially antagonized the cytosol-mediated protection (15 ؎ 5 and 9 ؎ 2% decrease in active force, p < 0.05). Quantitation of PKC isoform expression revealed the dominance of the Ca 2؉ -dependent PKC␣ over PKC␦ and PKC⑀ (189 ؎ 31, 7 ؎ 3, and 7 ؎ 2 ng/mg protein, respectively). Ca 2؉ stimulations of reconstituted human cardiomyocytes resulted in the translocation of endogenous PKC␣, but not PKC␤1, ␦, and ⑀ from the cytosol to the contractile system (PKC␣ association: control, 5 ؎ 3 arbitrary units; ؉Ca ). Our data suggest that PKC␣ translocates to the contractile system and anchors to TnI in a Ca 2؉ -dependent manner in the human heart, contributing to the maintenance of contractile force. Protein kinase C (PKC)3 is a family of serine/threonine kinases (1). Multiple PKC isozymes are often expressed in the same cell, mediating specific functions. Conventional and novel PKCs can be activated by lipids, like the endogenous diacylglycerol (DAG) or the exogenous phorbol ester PMA. It was reported decades ago that PMA activation of PKC leads to the translocation of PKC from the soluble to the particulate fraction (2). This observation has been confirmed by later works, and some of the binding proteins for activated PKC isozymes were identified (receptors for activated C kinases) (3, 4). Binding to its respective receptors for activated C kinase localizes each PKC isozyme in the vicinity of a subset of substrates and away from others, and hence this spatial organization may well explain the specificity of PKC isozymes in their intracellular signaling.It is of interest that from the many PKC isozymes expressed in the heart (5), PKC␣ is the single isozyme that translocates to the contractile system upon Ca 2ϩ stimulation in the rat heart (6), suggesting a unique physiological role for PKC␣ in the Ca 2ϩ -dependent regulation of myofibrillar contractility. As a matter of fact, PKC␣ has been implicated in models of ischemic heart failure, myocardial hypertrophy, hypertension, and atherosclerosis (7). In addition, PKC-dependent phosphorylation of myofibrillar proteins such as desmin (8), myosin light chain (9), troponin I (TnI), and troponin T (TnT) (10) has been documented with suggested functional consequences ranging from changes in mechanical integrity of the cardiac sarcomere to decreased actin-myosin ATPase activity and force generation.Long term activation of PKC is an essential step in ischemic preconditioning (11), a...

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