Propofol’ün, TRPM2 Katyon Kanalını Bastırarak Sisplatin Kaynaklı Oksidatif Nörotoksisiteye Karşı Nöroprotektif Etkisi

Öz

Amaç: Sisplatin (CPS), TRPM2 kanalını aktive ederek tümör hücrelerinde oksidan ve apoptotik etki meydana getirmesine rağmen bu etkilerin sinir hücrelerindeki yan etkilerinden dolayı CSP kullanımını sınırlandırmaktadır. Propofol (PRPF) mitokondriyal reaktif oksijen türleri (ROS) ve aşırı Ca+2 girişine bağlı apoptozisi düzenleyerek antioksidan ve nöroprotektif etki göstermektedir. Bununla birlikte, PRPF’un TRPM2 kanalını düzenleyerek antioksidan ve anti-apoptotik etki meydana getirebileceği insan SH-SY5Y sinir hücrelerinde henüz araştırılmamıştır. Bu çalışmanın amacı PRPF tedavisinin TRPM2 kanalını düzenleyerek sinir hücre ölüm ve mitokondriyal ROS üretimi üzerindeki etkilerinin SH-SY5Y hücrelerinde araştırılmasıdır. Materyal ve Metot: SH-SY5Y hücrelerinde 5 ana grup oluşturulmuştur. Bu gruplar: Kontrol, PRPF (200 mM ve 24 saat), CSP (25 mM ve 24 saat), CSP + PRPF ve CSP + TRPM2 kanal blokörleri (25 mM ACA ve 100 mM 2APB). Bulgular: CSP inkübasyonu, TRPM2 kanalını uyararak apoptosis, kaspaz -3, kaspaz -9, hücre ölümü yüzdesi, ROS, mitokondriyal hiperpolarizasyon, TRPM2 akım yoğunlukları ve hücre içi Ca+2 miktarı artırdı fakat hücre canlılığını azalttı. Bununla birlikte, PRPF, ACA ve 2APB tedavileri sonraları bu değerler normal değerlerine döndüler. Sonuç: PRPF tedavisi TRPM2 kanalı inhibe ederek CSP neden olduğu mitokondriyal oksidan ve apoptotik etkileri azalttı. PRPF tedavisi, CSP neden olduğu mitokondriyal oksidatif stres ve sinir hücre harabiyetini önlemede potansiyel kaynak olarak gözükmektedir.

Anahtar Kelimeler

• Oksidatif stres
• propofol
• sinir hasarı
• sisplatin
• TRPM2 kanalı

Propofol's Neuroprotective Effect Against Cisplatin-Induced Oxidative Neurotoxicity Via Suppression of the TRPM2 Cation Channel

Abstract

Objective: Cisplatin (CSP) exhibits strong oxidant and apoptotic effects in tumors, but it also causes adverse neurodegenerative effects by stimulating the TRPM2 cation channel. By regulating mitochondrial reactive free oxygen species (ROS) and excessive Ca2+ entry-mediated apoptosis, propofol (PRPF) exhibits antioxidant and neuroprotective properties. However, the action of the TRPM2 in these productions in human SH-SY5Y neuronal cells has not yet been determined. In SH-SY5Y, I investigated the protective effects of PRPF by modifying TRPM2, which affects CSP-induced neuronal mitochondrial function and death. Materials and Methods: I generated five main groups in the SH-SY5Y as control, PRPF (200 mM for 24h), CSP (25 mM for 24h), CSP + PRPF, and CSP + TRPM2 channel antagonists (25 mM ACA and 100 mM 2APB). Results: Through TRPM2 stimulation, the incubation with CSP increased the amounts of apoptosis, caspase -3, caspase -9, cell death percentage, ROS, mitochondrial hyperpolarization, TRPM2 current densities, and intracellular free Ca2+. However, the incubation of PRPF through the inhibition of TRPM2 decreased the amounts of these processes. Conclusions: PRPF treatment via TRPM2 suppression decreased the levels of mitochondrial oxidative stress and neuronal death caused by CSP. One effective therapy option for CSP-induced mitochondrial oxidative neuronal damage is the PRPF.

Keywords

• Cisplatin
• neuronal injury
• oxidative stress
• propofol
• TRPM2 channel

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