Neuroprotective effects of (24R)-1,24-dihydroxycholecalciferol in human neuroblastoma SH-SY5Y cell line.
The active form of Vitamin D(3) has been reported to prevent neuronal damage caused by a variety of insults, however, it may also induce undesirable hypercalcemic effects. In the present study, we evaluated effects of (24R)-1,24-dihydroxycholecalciferol (PRI-2191) on hydrogen peroxide- and excitatory amino acid-induced neuronal damage in human neuroblastoma (SH-SY5Y) cell line. Exposure of SH-SY5Y cells to N-methyl-d-aspartate (NMDA; 5mM), kainate (0.2mM) and hydrogen peroxide (0.1-1mM) significantly enhanced lactate dehydrogenase release. Furthermore, the neurotoxic effects of hydrogen peroxide was dependent on c-Jun N-terminal kinase (JNK)- and p38- mitogen-activated protein kinase (MAPK) activity. Both secosteroids at nanomolar concentrations inhibited neuronal damage, but their efficacy varied depending on the toxic agent. PRI-2191 was equipotent as 1alpha,25-dihydroxyVitamin D(3) in protecting SH-SY5Ycells against NMDA toxicity, and had stronger effect against hydrogen peroxide-induced damage, but was less efficient against kainate-induced injury. The obtained results suggest potential usefulness of PRI 2191 in the treatment of neurodegenerative diseases.
Tetich
M
M
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smêtna Street, 31-343 Kraków, Poland.
Kutner
A
A
Leskiewicz
M
M
Budziszewska
B
B
Lasoń
W
W
D045744:Cell Line, Tumor; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*
D004100:Dihydroxycholecalciferols; D018696:Neuroprotective Agents; C023850:1 alpha,24-dihydroxyvitamin D3