Inhibitions of anandamide transport and FAAH synthesis decrease apoptosis and oxidative stress through inhibition of TRPV1 channel in an in vitro seizure model
Yazarlar (4)
Mustafa Nazıroğlu Süleyman Demirel Üniversitesi, Türkiye
Afife Nur Taner
Süleyman Demirel University, Faculty Of Medicine, Türkiye
Süleyman Demirel University, Faculty Of Medicine, Türkiye
Esra Balbay
Süleyman Demirel University, Faculty Of Medicine, Türkiye
Süleyman Demirel University, Faculty Of Medicine, Türkiye
Doç. Dr. Bilal ÇİĞ Süleyman Demirel Üniversitesi, Türkiye
| Makale Türü | Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale) | ||
| Dergi Adı | Molecular and Cellular Biochemistry (Q2) | ||
| Dergi ISSN | 0300-8177 Wos Dergi Scopus Dergi | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | İngilizce | Basım Tarihi | 08-2018 |
| Cilt / Sayı / Sayfa | 453 / 1 / 143–155 | DOI | 10.1007/s11010-018-3439-0 |
| Makale Linki | https://doi.org/10.1007/s11010-018-3439-0 | ||
| Özet |
| Abstract: 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 Ca 2+ 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 Ca 2+ 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. Graphical abstract: Possible molecular pathways of involvement of capsazepine (CPZ) and AM4040 in anandamide and capsaicin (CAP)-induced apoptosis, oxidative stress, and Ca 2+ accumulation through TRPV1 channel in the seizure-induced rat hippocampus and human glioblastoma neurons. The TRPV1 channel is activated by different stimuli including reactive oxygen species (ROS), anandamide (AEA), and CAP and it is blocked by capsazepine (CPZ). Cannabinoid receptor type 1 (CB1) is also activated by AEA. The AEA levels in cytosol are decreased by fatty acid amide hydrolase (FAAH) enzyme. Inhibition of FAAH through URB597 induces stimulation of CB1 receptor through accumulation AEA. URB597 acts antiepileptic effects through inhibition of TRPV1. Overloaded Ca 2+ concentration of mitochondria can induce an apoptotic program by stimulating the release of apoptosis-promoting factors such as caspases 3 and caspase 9 by generating ROS due to respiratory chain damage. AM404 and CPZ reduce TRPV1 channel activation and Ca 2+ entry in the in vitro 4-AP seizure model-induced hippocampal and glioblastoma neurons. [Figure not available: see fulltext.]. |
| Anahtar Kelimeler |
| Anandamide | Apoptosis | Epilepsy | FAAH inhibition | Oxidative stress | TRPV1 |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| WoS | 36 |
| SCOPUS | 38 |