Resistance to hypoxia-induced, BNIP3-mediated cell death contributes to an increase in a CD133-positive cell population in human glioblastomas in vitro

01.12.2012

Kahlert UD, Maciaczyk D, Dai F, Claus R, Firat E, Doostkam S, Bogiel T, Carro MS, Döbrössy M, Herold-Mende C, Niedermann G, Prinz M, Nikkhah G, Maciaczyk J.

J Neuropathol Exp Neurol. 2012;71(12):1086-1099.

J Neuropathol Exp Neurol.          online article

We investigated the mechanisms responsible for hypoxia-dependent induction of CD133-positive BTSCs in glioblastomas. We confirmed that cultures exposed to lowered oxygen levels showed a severalfold increase of CD133-positive BTSCs. Both the increase of CD133-positive cells and deceleration of the growth kinetics were reversible after transfer to normoxic conditions. Exposure to hypoxia induced BNIP3 (BCL2/adenovirus E1B 19-kDa proteinYinteracting protein 3)Ydependent apoptosis preferentially in CD133-negative cells. Thus, epigenetic modifications led to their better survival in lowered oxygen tension.