scholarly journals Histidyl-Proline Diketopiperazine Isomers as Multipotent Anti-Alzheimer Drug Candidates

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 737 ◽  
Author(s):  
Hasan Turkez ◽  
Ivana Cacciatore ◽  
Mehmet Enes Arslan ◽  
Erika Fornasari ◽  
Lisa Marinelli ◽  
...  
Keyword(s):  
Cell Line ◽  
Human Lymphocytes ◽  
Neuroblastoma Cell ◽  
Disease Model ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Gene Expressions ◽  
Damage Potential ◽  
Human Neuroblastoma

Cyclic dipeptides administered by both parenteral and oral routes are suggested as promising candidates for the treatment of neurodegeneration-related pathologies. In this study, we tested Cyclo (His-Pro) isomers (cHP1-4) for their anti-Alzheimer potential using a differentiated human neuroblastoma cell line (SH-SY5Y) as an Alzheimer’s disease (AD) experimental model. The SH-SY5Y cell line was differentiated by the application of all-trans retinoic acid (RA) to obtain mature neuron-like cells. Amyloid-beta 1-42 (Aβ1-42) peptides, the main effector in AD, were administered to the differentiated cell cultures to constitute the in vitro disease model. Next, we performed cell viability analyses 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays) to investigate the neuroprotective concentrations of cyclodipeptides using the in vitro AD model. We evaluated acetylcholinesterase (AChE), α- and β-secretase activities (TACE and BACE1), antioxidant potency, and apoptotic/necrotic properties and performed global gene expression analysis to understand the main mechanism behind the neuroprotective features of cHP1-4. Moreover, we conducted sister chromatid exchange (SCE), micronucleus (MN), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) analyses to evaluate the genotoxic damage potential after applications with cHP1-4 on cultured human lymphocytes. Our results revealed that cHP1-4 isomers provide a different degree of neuroprotection against Aβ1-42-induced cell death on the in vitro AD model. The applications with cHP1-4 isomers altered the activity of AChE but not the activity of TACE and BACE1. Our analysis indicated that the cHP1-4 increased the total antioxidant capacity without altering total oxidative status levels in the cellular AD model and that cHP1-4 modulated the alterations of gene expressions by Aβ1-42 exposure. We also observed that cHP1-4 exhibited noncytotoxic and non-genotoxic features in cultured human whole blood cells. In conclusion, cHP1-4 isomers, especially cHP4, have been explored as novel promising therapeutics against AD.

scholarly journals Inhibition of the SK-N-MC human neuroblastoma cell line in vivo and in vitro by a novel nutrient mixture

2013 ◽  
Vol 29 (5) ◽  
pp. 1714-1720 ◽  
Author(s):  
M. WAHEED ROOMI ◽  
TATIANA KALINOVSKY ◽  
NUSRATH W. ROOMI ◽  
ALEKSANDRA NIEDZWIECKI ◽  
MATTHIAS RATH
Keyword(s):  
Cell Line ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Human Neuroblastoma Cell Line

Functional Changes in Potassium Conductances of the Human Neuroblastoma Cell Line SH-SY5Y During In Vitro Differentiation

1998 ◽  
Vol 79 (2) ◽  
pp. 648-658 ◽  
Author(s):  
Patrizia Tosetti ◽  
Vanni Taglietti ◽  
Mauro Toselli
Keyword(s):  
Steady State ◽  
Cell Line ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Human Neuroblastoma Cell Line ◽  
Differentiated Cells ◽  
Voltage Dependent

Tosetti, Patrizia, Vanni Taglietti, and Mauro Toselli. Functional changes in potassium conductances of the human neuroblastoma cell line SH-SY5Y during in vitro differentiation. J. Neurophysiol. 79: 648–658, 1998. The electrophysiological properties of voltage-dependent outward currents were investigated under voltage-clamp conditions in the human neuroblastoma cell line SH-SY5Y before and after in vitro differentiation with retinoic acid, by using the whole cell variant of the patch-clamp technique. Voltage steps to depolarizing potentials from a holding level of −90 mV elicited, in both undifferentiated and differentiated cells, outward potassium currents that were blocked by tetraethylammonium, but were unaffected by 4-aminopyridine, cadmium, and by shifts of the holding potentials to −40 mV. These currents activated rapidly and inactivated slowly in a voltage-dependent manner. In undifferentiated cells the threshold for current activation was about −30 mV, with a steady-state half activation potential of 19.5 mV. Maximum conductance was 4.3 nS and mean conductance density was 0.34 mS/cm2. Steady-state half inactivation potential was −13.8 mV and ∼10% of the current was resistant to inactivation. Both activation and inactivation kinetics were voltage dependent. In differentiated cells the threshold for current activation was about −20 mV, with a half potential for steady-state activation of 37.0 mV. Maximum conductance was 15.2 nS and mean conductance density was 0.78 mS/cm2. Steady-state half inactivation potential was −9.7 mV and ∼37% of the current was resistant to inactivation. Both activation and inactivation kinetics were voltage dependent. This diversity in potassium channel properties observed between undifferentiated and differentiated cells was related to differences in cell excitability. Under current-clamp conditions, the action potential repolarization rate in differentiated cells was about threefold faster than that of the abortive action potentials elicitable in undifferentiated cells. Furthermore, during prolonged stimulation, trains of spikes could be generated in some differentiated cells but not in undifferentiated cells.

Toxicity of Ethylene-bis-dithiocarbamates (EBDCs) in a Human Neuroblastoma Cell Line

1991 ◽  
Vol 19 (1) ◽  
pp. 39-40
Author(s):  
Dario Cova ◽  
Pietro Fumagalli ◽  
Angela Santagostino
Keyword(s):  
Cell Line ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Human Cell Line ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Order Of Magnitude

The aim of our research was the in vitro evaluation of the neurotoxic effects of three EBDCs (Nabam, Zineb and Maneb) and ETU on SK-N-BE human neuroblastoma cells as a model for neurotoxicity in humans. The EC50 value was used as an index of the toxicities of these compounds. Since Zineb and Maneb contain zinc and manganese as cations, respectively, in order to determine the contributions of these metals, the EC50s of zinc chloride and manganese chloride were also evaluated. Nabam, Zineb and Maneb had EC50 values ranging from 1μM to 30μM; the EC50s of manganese and zinc in this human cell line were found to be of the same order of magnitude as those of the EBDC fungicides. These in vitro effects are discussed in relation to the possible use of neuronal cell lines for detecting the neurotoxicities of these compounds.

Sign in / Sign up

Export Citation Format

Share Document