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Effects of neurosteroids on hydrogen peroxide‐ and staurosporine‐induced damage of human neuroblastoma SH‐SY5Y cells
Author(s) -
Leskiewicz M.,
Regulska M.,
Budziszewska B.,
Jantas D.,
JaworskaFeil L.,
BastaKaim A.,
Kubera M.,
Jagla G.,
Nowak W.,
Lason W.
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21591
Subject(s) - neuroactive steroid , staurosporine , pregnenolone sulfate , neuroprotection , dehydroepiandrosterone , mapk/erk pathway , sh sy5y , pregnenolone , chemistry , endocrinology , dehydroepiandrosterone sulfate , protein kinase a , medicine , pharmacology , kinase , biology , biochemistry , cell culture , neuroblastoma , steroid , receptor , genetics , hormone , gabaa receptor , androgen
Neurosteroids are important regulators of central nervous system function and may be involved in processes of neuronal cell survival. This study was undertaken to test the effect of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), pregnenolone (PGL), pregnenolone sulfate (PGLS), and allopregnanolone (Allo) on hydrogen peroxide‐ and staurosporine‐induced toxicity in SH‐SY5Y cells. It has been found that DHEAS inhibited the hydrogen peroxide toxicity in a concentration‐dependent manner, whereas DHEA was active only at higher doses. PGL and PGLS showed neuroprotective effects only at the lowest concentration. Allo had no significant effect on hydrogen peroxide‐evoked lactate dehydrogenase release and at the highest concentration aggravated its toxic effects. Next part of this study evaluated neurosteroid effects on staurosporine‐induced apoptosis. DHEAS, DHEA, and PGL significantly antagonized effects of staurosporine on both caspase‐3 activity and mitochondrial membrane potential. PGLS and Allo inhibited the staurosporine‐induced changes in both apoptotic parameters only at the lowest concentration. Antiapoptotic properties of neurosteroids were positively verified by Hoechst staining. Furthermore, as shown by calcein assay, DHEA, DHEAS, and PGL increased viability of staurosporine‐treated cells, and these effects were attenuated by specific inhibitors of phosphatidylinositol 3‐kinase (PI3‐K) and extracellular signal‐regulated protein kinase (ERK)‐mitogen activated protein kinase (MAPK). These data indicate that neurosteroids prevent SH‐SY5Y cell damage related to oxidative processes and activation of mitochondrial apoptotic pathway. Moreover, neuroprotective effects of DHEA, DHEAS seem to depend on PI3‐K and ERK/MAPK signaling pathways. It can be suggested that, at physiological concentrations, all studied neurosteroids participate in the inhibition of neuronal apoptosis, but with various potencies. © 2008 Wiley‐Liss, Inc.