Naslov
Protective effect of 20-HETE inhibition in a model of oxygen-glucose deprivation in N27 neuronal cells
(Protective effect of 20-HETE inhibition in a model of oxygen-glucose deprivation in N27 neuronal cells)

Autori
Poljak, Ljiljana ; Boban, Mirta ; Falck, John R ; Renić, Marija

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
8th Croatian neuroscience congress : book of abstract / - Zagreb, 2021, 112-112

Skup
8th Croatian neuroscience congress

Mjesto i datum
Online, 24.09.2021. - 25.09.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
20-HETE ; oxygen-glucose deprivation ; neuroprotection

Sažetak
20-Hydroxyeicosatetraenoic acid (20-HETE), a potent vasoconstrictor, is a cytochrome P-450 (CYP)-derived metabolite of arachidonic acid. Inhibitors of 20-HETE synthesis and/or actions have been reported to protect brain from ischemic stroke in the rat and primate. The neuroprotective effects were not associated with an increase in cerebral blood flow suggesting that these drugs may enhance the survival of neurons after ischemic injury independent of their effect on cerebral blood flow. In this regard, our previous study has demonstrated that 20-HETE directly promote neuronal injury in organotypic hippocampal slices subjected to oxygen-glucose deprivation (OGD) and that inhibitors of 20-HETE synthesis protect neurons from OGD-induced cell death by decreasing ROS formation and activation of caspase-3. In line with our findings, protective effect of 20-HETE inhibition has also been reported in mouse cortical neurons after OGD. In the present study we used N27 rat dopaminergic neuronal cells subjected to OGD followed by reoxygenation to examine whether 20-HETE contributes to ischemic injury through activation of NADPH oxidase and increased superoxide production. The preliminary results indicate that cell viability after OGD increased after treatment with a 20-HETE synthesis inhibitor or an antagonist. Administration of a 20-HETE mimetic had the opposite effect and increased neuronal cell death after OGD. That effect was reversed by coadministration of a NADPH oxidase inhibitor, apocynin, suggesting that 20- HETE amplifies neuronal cell death by increasing oxidative stress through NADPH oxidase- dependent mechanisms. Further studies will be taken to elucidate the molecular mechanisms underlying the protective effect of 20-HETE inhibitors against OGD-induced neuronal injury.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA