Insulin-like growth factor-I is an osmoprotectant in human neuroblastoma cells.
A role in neuronal homeostasis is suggested by the persistent expression of the insulin-like growth factors in the adult nervous system. SH-SY5Y human neuroblastoma cells, a well-characterized in vitro model of human neurons, were used to investigate the effects of hyperosmotic stress on neurons. Neuronal DNA fragmentation was detected within 1 h and pyknotic nuclei were apparent in attached cells after 12 h of hyperosmotic stress. In parallel, flow cytometry measurements revealed a sudden increase in the rate of cells irreversibly undergoing programmed cell death after 12 h of hyperosmotic exposure. Insulin-like growth factor-I delayed the onset of a laddered DNA fragmentation pattern for 24 h and provided continuing protection against hyperosmotic exposure for 72 h. Amino acid uptake was decreased in hyperosmotic medium even in the presence of insulin-like growth factor-I; the protein synthesis inhibitor cycloheximide neither prevented the induction of programmed cell death nor interfered with the ability of insulin-like growth factor-I to act as an osmoprotectant in hyperosmotic medium. Cysteine and serine protease inhibitors each prevented DNA fragmentation under hyperosmotic conditions, suggesting that the osmoprotectant activity of insulin-like growth factor-I involves the suppression of protease activity. Collectively, these results indicate that insulin-like growth factor-I limits the death of neurons under stressful environmental conditions, suggesting that it may provide a candidate therapy in the treatment of hyperosmolar coupled neurological injury.
Matthews
C C
CC
Department of Neurology, University of Michigan, Ann Arbor 48109-0588, U.S.A.
Odeh
H M
HM
Feldman
E L
EL
D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D009994:Osmolar Concentration; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D004273:DNA, Neoplasm; D007334:Insulin-Like Growth Factor I