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Utilizza questo identificativo per citare o creare un link a questo documento:
http://hdl.handle.net/10761/3623
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Data: | 20-feb-2017 |
Autori: | Heiss, Kathrin |
Titolo: | Role of pentazocine in an in vitro model of hypoxia/reoxygenation |
Abstract: | Experimental research is making considerable efforts to understand the rules that regulate
the balance between toxic and protective brain innate immunity. Sigma-1 receptor is
expressed in both neurons and glia is a unique class of intracellular proteins and is
involved in neurodegeneration. Our aim was to evaluate the biological effects of sigma-1 selective ligands, and bifunctional sigma-1 selective ligands conjugated with lipoil
function in microglia following hypoxia/reoxygenation condition. BV2 cells were exposed
to 3 hours of hypoxia and 24h of reoxygenation. Cells were treated with sigma-1 agonist
(+)-Pentazocine, various bifunctional sigma-1 agonists conjugated with lipoil function and
with lipoic acid alone. We assessed cell viability, apoptosis, reactive oxygen species (ROS)
formation, mitochondria membrane potential, and total thiol groups content (GSH). Our
results showed that 24h of reoxygenation resulted in a significant decrease of cell viability
and increase in apoptosis when compared to control. No significant effect of (+)Pentazocine and tested compounds was observed on cell viability following 24h of
reoxygenation. Furthermore, all treatments resulted in a significant decrease of ROS
formation when compared to untreated cells. Finally, pharmacological treatments restored
mitochondrial membrane potential when compared to the untreated group. Consistently
with these results we also showed that GSH content was restored following
pharmacological treatments. Our results showed that newly synthetized bifunctional
sigma-1 compounds exhibited significant antioxidant activity and induce apoptosis in
activated microglia thus providing a new tool for effective manipulation of brain
inflammation, with the specific aim of favoring its protective arm and boosting innate
neuroprotective mechanisms
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GENERAL INTRODUCTION MICROGLIA
The concept of microglia was introduced by Pio del Rio-Hortega as a defined cellular
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In | Area 06 - Scienze mediche
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