Glioblastoma Hücrelerinde Resveratrol Hipoksinin Neden Olduğu Apoptozis ve Oksidatif Nörotoksisite Artışlarını TRPA1 Katyon Kanalını Baskılayarak Azaltır

Abstract

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 azalışlarını artırdı. Sonuç: RES tedavisi, TRPA1 kanalını baskılayarak HPX'nin mitokondriyal oksidan ve sinir hücre apoptotik etkilerini azalttı. HPX neden olduğu mitokondriyal oksidatif stres ve sinir hücre harabiyetini önlemek için RES tedavisi potansiyel bir kaynak tedavi olarak gözükmektedir.

Keywords

• Apoptozis
• hipoksi
• mitokondriyal oksidatif stres
• resveratrol
• TRPA1 kanalı

Resveratrol Reduces Hypoxia-Caused Increases of Apoptosis and Oxidative Neurotoxicity via TRPA1 Cation Channel Suppression in Glioblastoma Cells

Abstract

Objective: Hypoxia (HPX) increases the amount of Ca2+ influx, apoptosis, and harmful free reactive oxygen species (ROS) in the 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 increased viable 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.

Keywords

• Apoptosis
• hypoxia
• mitochondrial oxidative stress
• resveratrol
• TRPA1 channel

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