PMID- 17447420 OWN - NLM STAT- MEDLINE DCOM- 20070517 LR - 20191026 IS - 0303-6995 (Print) IS - 0303-6995 (Linking) IP - 71 DP - 2006 TI - Isatin interaction with glyceraldehyde-3-phosphate dehydrogenase, a putative target of neuroprotective drugs: partial agonism with deprenyl. PG - 97-103 AB - There is evidence that the binding of deprenyl, a monoamine oxidase (MAO) B inhibitor, and other propargylamines to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is primarily responsible for their neuroprotective and antiapoptotic effects. Thus, GAPDH may be a target for other neuroprotective drugs. Using two independent approaches, radioligand analysis and an optical biosensor technique, we demonstrate here that GAPDH also interacts with the endogenous, reversible MAO B inhibitor, isatin. Deprenyl inhibited both [3H]isatin binding to GAPDH, and the binding of this enzyme to an isatin analogue, 5-aminoisatin, immobilized on to an optical biosensor cell. Another MAO inhibitor, tranylcypromine, was ineffective. Both deprenyl and isatin inhibited GAPDH-mediated cleavage of E. coli tRNA, and their effects were not additive. We suggest that isatin may be an endogenous partial functional agonist of deprenyl in its effect on GAPDH and GAPDH-mediated RNA cleavage. Changes in level of endogenous isatin may influence the neuroprotective effect of deprenyl in vivo. FAU - Medvedev, A AU - Medvedev A AD - Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia. Alexei.Medvedev@ibmc.msk.ru FAU - Buneeva, O AU - Buneeva O FAU - Gnedenko, O AU - Gnedenko O FAU - Fedchenko, V AU - Fedchenko V FAU - Medvedeva, M AU - Medvedeva M FAU - Ivanov, Y AU - Ivanov Y FAU - Glover, V AU - Glover V FAU - Sandler, M AU - Sandler M LA - eng GR - 072381/Z/03/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Austria TA - J Neural Transm Suppl JT - Journal of neural transmission. Supplementum JID - 0425126 RN - 0 (Monoamine Oxidase Inhibitors) RN - 0U46U6E8UK (NAD) RN - 10028-17-8 (Tritium) RN - 2K1V7GP655 (Selegiline) RN - 82X95S7M06 (Isatin) RN - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases) SB - IM MH - Animals MH - Biosensing Techniques/methods MH - Dose-Response Relationship, Drug MH - Drug Interactions MH - Glyceraldehyde-3-Phosphate Dehydrogenases/*metabolism MH - Isatin/*metabolism MH - Monoamine Oxidase Inhibitors/pharmacokinetics/*pharmacology MH - Muscles/chemistry MH - NAD/pharmacokinetics MH - Protein Array Analysis/methods MH - Protein Binding/drug effects MH - Rabbits MH - Selegiline/pharmacokinetics/*pharmacology MH - Time Factors MH - Tritium/metabolism EDAT- 2007/04/24 09:00 MHDA- 2007/05/18 09:00 CRDT- 2007/04/24 09:00 PHST- 2007/04/24 09:00 [pubmed] PHST- 2007/05/18 09:00 [medline] PHST- 2007/04/24 09:00 [entrez] AID - 10.1007/978-3-211-33328-0_11 [doi] PST - ppublish SO - J Neural Transm Suppl. 2006;(71):97-103. doi: 10.1007/978-3-211-33328-0_11.