otjhs Online Turkish Journal of Health Sciences 2459-1467 Oğuz KARABAY 10.26453/otjhs.1773319 Neurosciences (Other) Sinirbilim (Diğer) Glioblastoma Hücrelerinde Resveratrol Hipoksinin Neden Olduğu Apoptozis ve Oksidatif Nörotoksisite Artışlarını TRPA1 Katyon Kanalını Baskılayarak Azaltır Resveratrol Reduces Hypoxia-Caused Increases of Apoptosis and Oxidative Neurotoxicity via TRPA1 Cation Channel Suppression in Glioblastoma Cells https://orcid.org/0000-0002-0520-0672 Ertilav Kemal SÜLEYMAN DEMİREL ÜNİVERSİTESİ 12 20 2025 10 4 382 389 08 28 2025 10 27 2025 Copyright © 2016, Online Turkish Journal of Health Sciences 2016 Online Turkish Journal of Health Sciences

Amaç: Hipoksi (HPX), beyin ve sinir hücrelerinde Ca+2 girişi, apoptozis ve toksik reaktif oksijen türleri (ROS) oluşumunu artırır. Resveratrol (RES) voltaja duyarlı Ca+2 kanallarını bloke ederek ROS’un neden olduğu sinir hücre ölümünü azaltır. Bu çalışmanın amacı, HPX nedeniyle zarar gören SH-SY5Y sinir hücrelerinde, RES TRPA1 katyon kanalını inhibe ederek apoptozis ve ROS artışını nasıl etkilediğini SH-SY5Y glioblastoma sinir hücrelerinde araştırmaktır.Materyal ve Metot: SH-SY5Y hücreleri kontrol, RES (50 µM ve 24 saat), HPX (200 µM CoCl2 ve 24 saat) ve HPX + RES olacak şekilde dört gruba ayrıldı. Bulgular: CoCl2 ile inkübasyon, apoptotik (kaspaz-3, -8, ve -9) ve oksidan (ROS, mitokondriyal fonksiyon bozukluğu ve lipit peroksidasyon) düzeylerini artırdı. TRPA1 agonist (sinnamaldehit) inkübasyonu bu değerleri daha da artırdı. Bununla birlikte, TRPA1 antagonisti (AP-18) ve RES inkübasyonları bu artışları azalttı. AP-18 ve RES inkübasyonları, HPX inkübasyonunun neden olduğu hücre canlılığı yüzdesi, glutatyon miktarı ve glutatyon peroksidaz aktivitesi azalışlarınıartırdı. Sonuç: RES tedavisi, TRPA1 kanalını baskılayarakHPX'nin mitokondriyal oksidan ve sinir hücre apoptotik etkileriniazalttı. HPX neden olduğu mitokondriyal oksidatif stres ve sinir hücre harabiyetini önlemek için RES tedavisi potansiyel bir kaynak tedavi olarak gözükmektedir.

Objective: Hypoxia (HPX) increases the amount of Ca2+ influx, apoptosis, and harmful free reactive oxygen species (ROS) inthe brain and neurons. Resveratrol (RES) has been shown to reduce these increases in ROS-damaged neuronal cells by inhibiting voltage-gated Ca2+ channels. The aim of the study was to ascertain whether RES could also inhibit the elevated ROS and apoptosis induced by HPX in SH-SY5Y glioblastoma cells via inhibiting TRPA1. Materials and Methods: In the SH-SY5Y, four primary groups were induced as control, RES (50 µM for 24h), HPX (200 µM CoCl2 for 24h), and HPX + RES.Results: While the incubations of the TRPA1 antagonist (AP-18) and RES decreased the HPX-mediated upregulations of apoptotic (caspase -3, -8, and -9) and oxidants (ROS, mitochondrial dysfunction, and lipid peroxidation) concentrations, the TRPA1 agonist (cinnamaldehyde) stimulation further increased these concentrations. The RES increasedviable cell percentage, glutathione concentration, and glutathione peroxidase activity, all of which were diminished by HPX. Conclusions: The concentrations of HPX-induced neuronal apoptosis and mitochondrial oxidative stress were reduced by RES treatment through TRPA1 inhibition. It seems that RES is a potential treatment option for HPX-induced mitochondrial oxidative neuronal injury.

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