MPP+-induced cytotoxicity in neuroblastoma cells: Antagonism and reversal by guanosine

Guanosine exerts neuroprotective effects in the central nervous system. Apoptosis, a morphological form of programmed cell death, is implicated in the pathophysiology of Parkinson’s disease (PD). MPP+, a dopaminergic neurotoxin, produces in vivo and in vitro cellular changes characteristic of PD, such as cytotoxicity, resulting in apoptosis. Undifferentiated human SH-SY5Y neuroblastoma cells had been used as an in vitro model of Parkinson’s disease. We investigated if extracellular guanosine affected MPP+-induced cytotoxicity and examined the molecular mechanisms mediating its effects. Exposure of neuroblastoma cells to MPP+ (10 μM–5 mM for 24–72 h) induced DNA fragmentation in a time-dependent manner (p < 0.05). Administration of guanosine (100 μM) before, concomitantly with or, importantly, after the addition of MPP+ abolished MPP+-induced DNA fragmentation. Addition of MPP+ (500 μM) to cells increased caspase-3 activity over 72 h (p < 0.05), and this was abolished by pre- or co-treatment with guanosine. Exposure of cells to pertussis toxin prior to MPP+ eliminated the anti-apoptotic effect of guanosine, indicating that this effect is dependent on a Gi protein-coupled receptor, most likely the putative guanosine receptor. The protection by guanosine was also abolished by the selective inhibitor of the enzyme PI-3-K/Akt/PKB (LY294002), confirming that this pathway plays a decisive role in this effect of guanosine. Neither MPP+ nor guanosine had any significant effect on α-synuclein expression. Thus, guanosine antagonizes and reverses MPP+-induced cytotoxicity of neuroblastoma cells via activation of the cell survival pathway, PI-3-K/Akt/PKB. Our results suggest that guanosine may be an effective pharmacological intervention in PD

FEM analysis of GFRP single cell test beam and modified GFRP bridge deck.

This document contains the details of the Finite Element Analysis of a single cell Glass Fibre Reinforced Plastic (GFRP) test beam and the modified GFRP bridge deck. These analytical studies have been carried out to know the magnitude of the stress in probable failure zones and to study the overall behaviour of structure under full scale static loading. A general purpose FEM package NASTRAN, has been used for analysis

Design of an architecture of a Production Planning and Control System (PPC) for Additive Manufacturing (AM)

Additive Manufacturing is increasingly used in the industrial sector as a result of continuous development. In the Production Planning and Control (PPC) system, AM enables an agile response in the area of detailed and process planning, especially for a large number of plants. For this purpose, a concept for a PPC system for AM is presented, which takes into account the requirements for integration into the operational enterprise software system. The technical applicability will be demonstrated by individual implemented sections. The presented solution approach promises a more efficient utilization of the plants and a more elastic use