title: Dipeptidyl compounds ameliorate the serum-deprivation-induced reduction in cell viability via the neurotrophin-activating effect in SH-SY5Y cells.
abstract: OBJECTIVE
  We have searched for low-molecular-weight compounds as potent new non-immunosuppressive immunophilin ligands (NI-IPLs) that are stronger than existent NI-IPLs such as GPI1046 and/or V10367 from the perspective of neuroprotective efficacy. We selected six dipeptidyl compounds as new NI-IPL candidates, and first examined the effects of each of these compounds on the serum-deprivation-induced reduction in the viability of SH-SY5Y cells. In addition, we clarified the effects of these compounds on neurotrophin release into medium in SH-SY5Y cells.
  
  
  RESULTS
  Pre-treatment with Leu-Ile and Ile-Ile prevented the serum deprivation-induced reduction in cell viability in SH-SY5Y cells. In naive SH-SY5Y cells, treatment with Leu-Ile and Ile-Ile for 24 hours significantly increased both brain-derived neurotrophic factor and glial cell-line-derived neurotrophic factor releases in comparison with relative vehicle treatments. Moreover, none of the dipeptidyl compounds could prevent the concanavalin A-induced enhancement in interleukin-2 and interleukin-4 release in mouse spleen cells.
  
  
  CONCLUSIONS
  The immunosuppressive effect is not essential to the neuroprotective properties of dipeptidyl compounds, and Leu-Ile and Ile-Ile have neurotrophin-activating effects, like FK506 and its existing non-immunosuppressive derivatives.
authors: Department of Clinical Pharmacy, Shujitsu University School of Pharmacy, Okayama, Japan. tanaka-ken-ichi@spu.ac.jp
authors: Ken-ichi
authors: K
authors: Tanaka
authors: Hiroya
authors: H
authors: Ogo
authors: Hiroaki
authors: H
authors: Kaji
authors: Kaori
authors: K
authors: Miyatake
authors: Erika
authors: E
authors: Tokudome
authors: Kanako
authors: K
authors: Sonoda
authors: Norio
authors: N
authors: Ogawa
authors: Masato
authors: M
authors: Asanuma
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*
chemical_list: D004151:Dipeptides; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents