Paclitaxel inhibits the activity and membrane localization of PKCα and PKCβI/II to elicit a decrease in stimulated calcitonin gene-related peptide release from cultured sensory neurons

Peripheral neuropathy is a dose-limiting and debilitating side effect of the chemotherapeutic drug, paclitaxel. Consequently, elucidating the mechanisms by which this drug alters sensory neuronal function is essential for the development of successful therapeutics for peripheral neuropathy. We previously demonstrated that chronic treatment with paclitaxel (3–5 days) reduces neuropeptide release stimulated by agonists of TRPV1. Because the activity of TRPV1 channels is modulated by conventional and novel PKC isozymes (c/nPKC), we investigated whether c/nPKC mediate the loss of neuropeptide release following chronic treatment with paclitaxel (300 nM; 3 and 5 days). Release of the neuropeptide, calcitonin gene-related peptide (CGRP), was measured as an index of neuronal sensitivity. Following paclitaxel treatment, cultured dorsal root ganglia sensory neurons were stimulated with a c/nPKC activator, phorbol 12,13-dibutyrate (PDBu), or a TRPV1 agonist, capsaicin, in the absence and presence of selective inhibitors of conventional PKCα and PKCβI/II isozymes (cPKC). Paclitaxel (300 nM; 3 days and 5 days) attenuated both PDBu- and capsaicin-stimulated release in a cPKC-dependent manner. Under basal conditions, there were no changes in the protein expression, phosphorylation or membrane localization of PKC α, βI or βII, however, paclitaxel decreased cPKC activity as indicated by a reduction in the phosphorylation of cPKC substrates. Under stimulatory conditions, paclitaxel attenuated the membrane translocation of phosphorylated PKC α, βI and βII, providing a rationale for the attenuation in PDBu- and capsaicin-stimulated release. Our findings suggest that a decrease in cPKC activity and membrane localization are responsible for the reduction in stimulated peptide release following chronic treatment with paclitaxel in sensory neurons

Electron Self-Energy of High Temperature Superconductors as Revealed by Angle Resolved Photoemission

In this paper, we review some of the work our group has done in the past few years to obtain the electron self-energy of high temperature superconductors by analysis of angle-resolved photoemission data. We focus on three examples which have revealed: (1) a d-wave superconducting gap, (2) a collective mode in the superconducting state, and (3) pairing correlations in the pseudogap phase. In each case, although a novel result is obtained which captures the essense of the data, the conventional physics used leads to an incomplete picture. This indicates that new physics needs to be developed to obtain a proper understanding of these materials.Comment: 5 pages, revtex, 3 encapsulated postscript figures, SNS97 proceeding

Ginzburg-Landau Expansion and the Slope of the Upper Critical Field in Disordered Superconductors with Anisotropic Pairing

It is demonstrated that the slope of the upper critical field $|dH_{c2}/dT|_{T_{c}}$ in superconductors with $d$-wave pairing drops rather fast with concentration of normal impurities, while in superconductors with anisotropic $s$-wave pairing $|dH_{c2}/dT|_{T_{c}}$ grows, and in the limit of strong disorder is described by the known dependences of the theory of ``dirty'' superconductors. This allows to use the measurements of $H_{c2}$ in disordered superconductors to discriminate between these different types of pairing in high-temperature and heavy-fermion superconductors.Comment: 7 pages, 5 figures, RevTeX 3.0, 4 Postscript figures attached; Submitted to JETP Letter

On the possibility of superconductivity in PrBa2Cu3O7

Recent reports about observations of superconductivity in PrBa2Cu3O7 raise a number of questions: (i) of various theories striving to explain the Tc suppression in PrxY{1-x}Ba2Cu3O7, are there any compatible with possible superconductivity in stoichiometric PrBa2Cu3O7? (ii) if this superconductivity is not an experimental artifact, are the superconducting carriers (holes) of the same character as in the other high-Tc cuprates, or do they represent another electronic subsystem? (iii) is the underlying mechanism the same as in other high-Tc superconductors? I present an answer to the first two questions, while leaving the last one open.Comment: 4 pages 4 eps fig

Effect of non-magnetic impurities on the gap of a dx2−y2d_{x^2-y^2} superconductor as seen by angle-resolved photoemission

An analysis of angle-resolved photoemission (ARPES) experiments in the superconducting state of the high \tc copper-oxides is presented. It is based on a phenomenological weak-coupling BCS model which incorporates the experimental normal state dispersion extracted from ARPES, and non-magnetic impurity scattering in the presence of a $d_{x^2-y^2}$ order parameter (OP). It is shown, that already in the pure case, the broadening by finite momentum resolution of the analyzer leads to a finite region of apparent `gaplessness' around the true node of the OP. Non-magnetic impurities further amplify this effect by introducing additional spectral weight around zero frequency. At sufficiently large impurity concentrations $n_i\approx 0.02-0.05$, this results in an extended region of `gaplessness' up to $\delta\phi=\pm7$ ($\phi$ the angle on the Fermi surface) around the true node for a large range of moderate to strong impurity potential strengths. Different ways to identify the presence of impurity scattering in the ARPES spectra are proposed.Comment: 8 pages uuencoded gzipped Postscrip

Superconductivity in Pr2Ba4Cu7O15-delta with metallic double chains

We report superconductivity with $T_{c,onset}$=$\sim$10K in Pr$_{2}$Ba$_{4}$Cu$_{7}$O$_{15-\delta}$ compound possessing metallic double chains. A reduction treatment on as-sintered samples causes not only the enhanced metallic conduction but also the appearance of superconductivity accompanied by the c-axis elongation due to oxygen deficiency