img
Inhibitions of anandamide transport and FAAH synthesis decrease apoptosis and oxidative stress through inhibition of TRPV1 channel in an in vitro seizure model     
Yazarlar
Mustafa Nazıroğlu
Süleyman Demirel Üniversitesi, Türkiye
Afife Nur Taner
Esra Balbay
Doç. Dr. Bilal ÇİĞ Doç. Dr. Bilal ÇİĞ
Süleyman Demirel Üniversitesi, Türkiye
Özet
The expression level of TRPV1 is high in hippocampus which is a main epileptic area in the brain. In addition to the actions of capsaicin (CAP) and reactive oxygen species (ROS), the TRPV1 channel is activated in neurons by endogenous cannabinoid, anandamide (AEA). In the current study, we investigated the role of inhibitors of TRPV1 (capsazepine, CPZ), AEA transport (AM404), and FAAH (URB597) on the modulation of Ca2+ entry, apoptosis, and oxidative stress in in vitro seizure-induced rat hippocampus and human glioblastoma (DBTRG) cell line. The seizure was induced in the hippocampal and DBTRG neurons using in vitro 4-aminopyridine (4-AP) to trigger a seizure-like activity model. CPZ and AM404 were fully effective in reversing 4-AP-induced intracellular free Ca2+ concentration of the hippocampus and TRPV1 current density of DBTRG. However, AEA and CAP did not activate TRPV1 in the URB597-treated neurons. Hence, we observed TRPV1 blocker effects of URB597 in the DBTRG neurons. In addition, the AM404 and CPZ treatments decreased intracellular ROS production, mitochondrial membrane depolarization, apoptosis, caspases 3 and 9 values in the hippocampus. In conclusion, the results indicate that inhibition of AEA transport, FAAH synthesis, and TRPV1 activity can result in remarkable neuroprotective effects in the epileptic neurons.
Anahtar Kelimeler
Anandamide | Apoptosis | Epilepsy | FAAH inhibition | Oxidative stress | TRPV1
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı MOLECULAR AND CELLULAR BIOCHEMISTRY
Dergi ISSN 0300-8177
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili İngilizce
Basım Tarihi 03-2019
Cilt No 453
Sayı 1
Sayfalar 143 / 155
Doi Numarası 10.1007/s11010-018-3439-0
Makale Linki http://dx.doi.org/10.1007/s11010-018-3439-0