No abstract

Protein kinase C (PKC), a family of 12 distinct serine-threonine kinases, is an important intracellular signaling pathway involved in various cellular functions, such as proliferation, hypertrophy, apoptosis, and adhesion. PKC-, a novel PKC isoform that is activated in the diabetic kidney, has been demonstrated to have a central role in the underlying signaling infrastructure of myocardial ischemia and hypertrophy. T he family of protein kinase C (PKC) includes at least 12 isoforms that can be divided in three subgroups, namely classical PKC (PKC-␣, PKC-␤1, PKC-␤2, and PKC-␥), novel PKC (PKC-␦, PKC-, PKC-, and PKC-), and atypical PKC (PKC-and PKC-/) (1). Each PKC isoform is a separate gene product, with the exception of PKC-␤1 and -␤2, which are alternative spliced variants of the same gene (1). PKC has been identified as the cellular receptor for the lipid second messenger diacylglycerol (DAG) and is therefore a key enzyme in the signaling mechanisms by activation of receptors that are coupled to phospholipase C, which leads to a transient elevation in DAG levels (1). Furthermore, PKC is a high-affinity receptor for phorbol ester tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (1). PKC isoforms display a distinct cell-and tissue-type expression pattern or intracellular localization that is considered for the multiplicity of the PKC isoforms (2,3). In particular, it has been demonstrated that the activation of PKC increases the production of the extracellular matrix (ECM) and various cytokines; enhances contractility, permeability, and vascular cell proliferation; induces the activation of cytosolic phospholipase A 2 ; and inhibits Na-ϩ K ϩ -ATPase (4,5). All of these events are important features of cardiovascular diseases such as diabetes, oxidative stress, and hypertension (4,5). Therefore, PKC is considered to play a pivotal role in intracellular signal modulation and interaction of metabolic and hemodynamic factors that lead to cardiovascular disease (4,5). Murine knockout (KO) models of various PKC isoforms now represent an exciting tool for studying in vivo effects of such single-gene deletions and how they contribute to the development of cardiovascular diseases such as diabetes and hypertension (6,7). We recently showed that deletion of PKC-␣ in vivo leads to protection against the development of albuminuria in streptozotocin (STZ)-induced diabetic mice, indicating a specific role of this classical isoform in the breakdown of the glomerular filtration barrier in the diabetic state (8). It is interesting that we failed to demonstrate a role for this PKC isoform in the development of TGF-␤ 1 -mediated renal hypertrophy in this KO mouse model (8). However, Klein et al. (9) recently demonstrated that deletion of PKC-, a novel PKC isoform that is postulated to be involved in the regulation of myocardial ischemia-reperfusion, leads to increased murine myocardial fibrosis in a chronic pressure overload model that is associated with diastolic dysfunction. Furthermore, a PKC--dependent Received Jul...

We study the quasi-instantaneous change of electron density in the unit cells of LiH and NaBH4 in response to a nonresonant strong optical field. We determine for the first time the related transient electron density maps, applying femtosecond x-ray powder diffraction as a structure probe. The light-induced charge relocation in NaBH4 exhibits an electron transfer from the anion (BH(4)(-)) to the Na(+) cation. In contrast, LiH displays the opposite behavior, i.e., an increase of the ionicity of LiH in the presence of the strong electric field. This behavior originates from strong electron correlations in LiH, as is evident from a comparison with quasiparticle band structures calculated within the Coulomb-hole-plus-screened-exchange formalism.

Table-top laser-driven hard x-ray sources with kilohertz repetition rates are an attractive alternative to large-scale accelerator-based systems and have found widespread applications in x-ray studies of ultrafast structural dynamics. Hard x-ray pulses of 100 fs duration have been generated at the Cu Kα wavelength with a photon flux of up to 109 photons per pulse into the full solid angle, perfectly synchronized to the sub-100-fs optical pulses from the driving laser system. Based on spontaneous x-ray emission, such sources display a particular noise behavior which impacts the sensitivity of x-ray diffraction experiments. We present a detailed analysis of the photon statistics and temporal fluctuations of the x-ray flux, together with experimental strategies to optimize the sensitivity of optical pump/x-ray probe experiments. We demonstrate measurements close to the shot-noise limit of the x-ray source.

Quantum theory has linked microscopic currents and macroscopic polarizations of ferroelectrics, but the interplay of lattice excitations and charge dynamics on atomic length and time scales is an open problem. Upon phonon excitation in the prototypical ferroelectric ammonium sulfate [(NH4)2SO4], we determine transient charge density maps by femtosecond x-ray diffraction. A newly discovered low frequency-mode with a 3 ps period and sub-picometer amplitudes induces periodic charge relocations over some 100 pm, a hallmark of soft-mode behavior. The transient charge density allows for deriving the macroscopic polarization, showing a periodic reversal of polarity.