Neuroprotective and antioxidant properties of FKBP-binding immunophilin ligands are independent on the FKBP12 pathway in human cells.
We focused on immunophilin isoforms in order to clarify the neuroimmunophilins which were identified as targets for the immunophilin ligands to elicit a neuroprotective effect. Although the expressions of five FK506-binding protein (FKBP) mRNAs were detected in both SH-SY5Y (human neuroblastoma) and U251 (human glioma) cell lysates, the FKBP12 mRNA expression was detected in only the SH-SY5Y cells, and not the U251 cells. However, we found that the SH-SY5Y and the U251 cells were equipotent in the intensity of cellular protection of FK506 (an immunosuppressive immunophilin ligand) and GPI1046 (a non-immunosuppressive FK506 analog), indicating that the protective effect and glutathione activation of FK506 and GPI1046 had little need to bind FKBP12. Therefore, we conclude that the neuroprotective and antioxidant properties of immunophilin ligands are independent on the FKBP12 pathway.
Tanaka
Ken-ichi
K
Department of Brain Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. kntanaka@cc.okayama-u.ac.jp
Fujita
Naoko
N
Higashi
Youichirou
Y
Ogawa
Norio
N
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003124:Colorimetry; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D019696:Peptidylprolyl Isomerase; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology*; D022061:Tacrolimus Binding Protein 1A / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000099159:Tacrolimus Binding Protein 5
D000199:Actins; D000975:Antioxidants; D004121:Dimethyl Sulfoxide; D005978:Glutathione; D006861:Hydrogen Peroxide; D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D019696:Peptidylprolyl Isomerase; D011759:Pyrrolidines; D012333:RNA, Messenger; D016559:Tacrolimus; D022061:Tacrolimus Binding Protein 1A; D022021:Tacrolimus Binding Proteins; D014404:Tubulin; D000099159:Tacrolimus Binding Protein 5; C104949:GPI 1046; C074856:FKBP3 protein, human; C403485:tacrolimus binding protein 4; C110054:FKBP10 protein, human