University of Zagreb. Faculty of Science. Department of Biology.
Abstract
Okadaična kiselina je selektivni inhibitor serin/treonin fosfataza (PP1 i PP2A) koje kataliziraju defosforilaciju tau proteina i pojačava ekspresiju gena cdk5 i p25. Cdk5 inhibira fosfataze i time inducira hiperfosforilaciju tau proteina. Okadaična kiselina potiče tau patologije gotovo identičnu onoj kod Alzheimerove bolesti (AB) in vivo i in vitro. Epigalokatehin-3-galat (EGCG) je flavonoid iz skupine flavonola. Nalazimo ga u zelenom čaju i i u brojnim in vitro pokusima su dokazana njegova neuroprotektivna svojstva. EGCG je antioksidans i ima protuupalna svojstva, a novija istraživanja pokazuju da je uključen u nekoliko neuroprotektivnih staničnih mehanizama. Cilj ovog rada je bio ustanoviti može li EGCG obustaviti staničnu smrt potaknutu okadaičnom kiselinom na modelu neuroblastomskih SH-SY5Y stanica i neurona dobivenih njihovom diferencijacijom. Utvrđeno je da EGCG u predtretmanu ili kotretmanu s okadaičnom kiselinom može zaustaviti njezino neurotoksično djelovanje neuroblastomske SH-SY5Y stanice i neurone dobivene njihovom diferencijacijom.Okadaic acid is a selective inhibitor of serine/threonine phosphatases (PP1 and PP2A) that catalyze dephpsphorylation of tau protein and induce cdk5 and p25 (first write in full) expression. Cdk5 inhibits phosphatases and induces hyperphosphorylation of tau protein. Okadaic acid induces pathological changes of tau protein in vivo and in vitro in a way similar to that seen in Alzheimer’s disease (AD). Epigallocatechin-3-gallate (EGCG) is flavonoid found in green tea and is considered as one of the potentially neuroprotective agents for AD. EGCG is antioxidant and anti-inflamatory agent, and recent studies showed that it has several neuroprotective mechanisms of action. The aim of this work was to find out if EGCG can stop cell death induced by okadaic acid in neuroblastoma cell line SH-SY5Y and neurons derived therefrom. We have shown that EGCG pre-treatment and co-treatment with okadaic acid can decrease okadaic acid toxicity neuroblastoma SH-SY5Y cells and neurons differentiated therefrom
