67 research outputs found
Endogenous prion protein conversion is required for prion-induced neuritic alterations and neuronal death
No full textInternational audiencePrions cause fatal neurodegenerative conditions and result from the conversion of host-encoded cellular prion protein (PrPC) into abnormally folded scrapie PrP (PrPSc). Prions can propagate both in neurons and astrocytes, yet neurotoxicity mechanisms remain unclear. Recently, PrPC was proposed to mediate neurotoxic signaling of beta-sheet-rich PrP and non-PrP conformers independently of conversion. To investigate the role of astrocytes and neuronal PrPC in prion-induced neurodegeneration, we set up neuron and astrocyte primary cocultures derived from PrP transgenic mice. In this system, prion-infected astrocytes delivered ovine PrPSc to neurons lacking PrPC (prion-resistant), or expressing a PrPC convertible (sheep) or not (mouse, human). We show that interaction between neuronal PrPC and exogenous PrPSc was not sufficient to induce neuronal death but that efficient PrPC conversion was required for prion-associated neurotoxicity. Prion-infected astrocytes markedly accelerated neurodegeneration in homologous cocultures compared to infected single neuronal cultures, despite no detectable neurotoxin release. Finally, PrPSc accumulation in neurons led to neuritic damages and cell death, both potentiated by glutamate and reactive oxygen species. Thus, conversion of neuronal PrPC rather than PrPC-mediated neurotoxic signaling appears as the main culprit in prion-induced neurodegeneration. We suggest that active prion replication in neurons sensitizes them to environmental stress regulated by neighboring cells, including astrocytes.-Cronier, S., Carimalo, J., Schaeffer, B., Jaumain, E., Beringue, V., Miquel, M.-C., Laude, H., Peyrin, J.-M. Endogenous prion protein conversion is required for prion-induced neuritic alterations and neuronal death. FASEB J. 26, 3854-3861 (2012). www.fasebj.or
Cellular prion protein directly interacts with and enhances lactate dehydrogenase expression under hypoxic conditions
No full textAlthough a physiological function of the cellular prion protein (PrPc) is still not fully clarified, a PrPc-mediated neuroprotection against hypoxic/ischemic insult is intriguing. After ischemic stroke prion protein knockout mice (Prnp(0/0)) display significantly greater lesions as compared to wild-type (WT) mice. Earlier reports suggested an interaction between the glycolytic enzyme lactate dehydrogenase (LDH) and PrPc. Since hypoxic environment enhances LDH expression levels and compels neurons to rely on lactate as an additional oxidative substrate for energy metabolism, we examined possible differences in LDH protein expression in WT and Prnp(0/0) knockout models under normoxic/hypoxic conditions in vitro and in vivo, as well as in a HEK293 cell line. While no differences are observed under normoxic conditions, LDH expression is markedly increased after 60-min and 90-min of hypoxia in WT vs. Prnp(0/0) primary cortical neurons with concurrent less hypoxia-induced damage in the former group. Likewise, cerebral ischemia significantly increases LDH levels in WT vs. Prnp(0/0) mice with accompanying smaller lesions in the WT group. HEK293 cells overexpressing PrPc show significantly higher LDH expression/activity following 90-min of hypoxia as compared to control cells. Moreover, a cytoplasmic co-localization of LDH and PrPc was recorded under both normoxic and hypoxic conditions. Interestingly, an expression of monocarboxylate transporter 1, responsible for cellular lactate uptake, increases with PrPc-overexpression under normoxic conditions. Our data suggest LDH as a direct PrPc interactor with possible physiological relevance under low oxygen conditions. (C) 2015 Published by Elsevier Inc
New method for calculating helicity amplitudes of jet-like QED processes for high-energy colliders
No full textAs a continuation of our previous paper [Eur. Phys. J. C 23, 633 (2002)] we further develop our new method for calculating helicity amplitudes of jet-like QED processes described by tree diagrams, applying it to lepton pair production. This method consists in replacing spinor structures for real and weakly virtual intermediate leptons by simple transition vertices. New vertices are introduced for the pair production case, and previous bremsstrahlung vertices are generalized to include virtual photons inside the considered jet. We present a diagrammatic approach that allows us to write down in an efficient way the leading helicity amplitudes, at tree level. The obtained compact amplitudes are particularly suitable for numerical calculations in jet-like kinematics. Several examples with up to four particles in a jet are discussed in detail
Prions et apoptose neuronale (étude des mécanismes moléculaires et cellulaires précoces)
No full textLes maladies à prions se caractérisent par la mort apoptotique des neurones centraux et par l accumulation cérébrale d une forme anormale de la PrPC appelée PrPSc. Nos travaux concernent les phases précoces de l apoptose, cibles thérapeutiques potentielles. Nos expériences de co-culture d astrocytes infectés et de neurones exprimant ou non la PrPC, démontrent que la présence de la PrPC neuronale homologue est indispensable à la neurotoxicité associée à l infection, et potentialisée par contact direct entre neurones et astrocytes. De plus, l infection augmente la sensibilité neuronale à un stress par le glutamate ou les radicaux libres. Nous montrons l activation subséquente du module JNK/c-Jun lors de l apoptose induite par un peptide modèle (PrP106-126) et après infection par les prions dans des neurones en culture. Enfin, nous décrivons des altérations neuritiques précoces qui pourraient être responsables de dysfonctionnements neuronaux à l origine des premiers signes cliniques ;PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF
Nuclei as generators of quasi-real photons
No full textAn equivalent photon approximation is tested for the inelastic scattering of high-energy non-hadronic particles (leptons and photons) in the electromagnetic field of nuclei. Coherent, incoherent elastic and incoherent inelastic contributions are included. As for the coherent (Coulomb) term, various nuclei (92U235, 27Co59, 6C12) with different types of form factors are considered. Four processes are considered : a) photoproduction of muon pairs ; b) muon bremsstrahlung ; c) muon trident producion (term with the time-like photon only) ; d) neutrinoproduction of a vector boson. The comparison of the approximation with the exact calculation is made for dσ/dW, where W is the invariant mass of the nonhadronic system produced. The approximation works well in general. As an application, we show the full calculation of the trident process (except for the correction due to the Pauli principle)
Towards a complete leptons Monte Carlo
No full text3 pages, 4 figures, presented at the PHOTON 99 conferenceInternational audienceThe total cross-section of the leptons process is known to have a large constant value at high energy, but a complete and exact calculation of related differential spectra does not exist yet. However a complete study of the process is important at NLC for luminosity measurements or for background estimations. We here report on our various steps in that direction, including the implementation of a first new calculation of helicity amplitudes in a Monte-Carlo generator
New method for calculating helicity amplitudes of jet-like QED processes for high-energy colliders II. Processes with lepton pair production
No full text11 pages, 11 figures, Latex, Springer-Latex macros includedAs continuation of our previous paper we further develop our new method for calculating helicity amplitudes of jet-like QED processes described by tree diagrams, applying it to lepton pair production. This method consists in replacing spinor structures for real and weakly virtual intermediate leptons by simple transition vertices. New vertices are introduced for the pair production case, and previous bremsstrahlung vertices are generalized to include virtual photons inside the considered jet. We present a diagrammatic approach that allows to write down in an efficient way the leading helicity amplitudes, at tree level. The obtained compact amplitudes are particularly suitable for numerical calculations in jet-like kinematics. Several examples with up to four particles in a jet are discussed in detail
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