Nörolojik Hücrelerde TRPM2 Katyon Kanallarının Moleküler Mekanizmalardaki Rolleri

Year 2010, Volume: 27 Issue: 4, 144 - 151, 16.02.2011

Cemil Özgül Mustafa Nazıroğlu

Abstract

Vücuttaki tüm organlar özellikle merkezi sinir sistemi, serbest radikal hasarına karşı duyarlıdır. Beynin yüksek oksijen tüketimi, kolayca okside olabilen zengin yağ asitlerini barındırması, diğer organlara göre düşük seviyede antioksidan enzim ve antioksidan içermesi onu serbest oksijen radikalleri tarafından birincil hedef haline getirmektedir. Na+ ve Ca+2 iyonlarına geçirgen melastatine bağlı “transient receptor potential 2 (TRPM2)” katyon kanalları ya Ca+2 ile uyum içinde olan ADP-riboz tarafından ya da oksidatif stres (H2O2) tarafından kanalların enzimatik Nudix bölgesine bağladığı ve ADP-riboz pirofosfataz’ın aktive olduğu rapor edilmiştir. Bu enzim aktivasyonu sonucunda da TRPM2 kanallarının açıldığı gözlemlenmiştir. Bu derleme çalışmasında, nöronal hücrelerde, TRPM2 inhibisyonuna yol açtığı düşünülen ADPR ve H2O2 maddeleri tam anlaşılmadığı için nörolojik hastalıklardaki bipolar hastalıklar kadar mikroglia, hipokampus ve beyindeki ADPR ve oksidatif stresin TRPM2 kanalları üzerindeki etkileri gözden geçirilmiştir. Mikroglia ve hipokampal hücrelerde TRPM2 katyon kanallarının hem ADPR hem de H2O2 tarafından açıldığı gözlemlendi. Buna ek olarak, nörolojik hastalıklarda H2O2 nin TRPM2 aktivasyonundan sorumlu olduğu gözüküyor. Bipolar hastalıkların etiyolojisinde genetik faktörler önemli rollere sahip olabilirler.

Keywords

TRPM2, Ca2+, neurological cells, oxidative stress, ADP- ribose, glial cells.

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