title: In vitro binding and in vivo biodistribution studies of the neuroprotective peptide humanin using [125I]humanin derivatives.
abstract: Humanin (HN) and HN-derivatives are a family of peptides first reported in the last decade with potent in vitro and in vivo neuroprotective activity, which is mediated through a not completely elucidated mechanism. Recently, our group has evaluated the effect of various HN-derivatives on the 3-quinuclidinyl benzilate (QNB)-induced impairment of spatial orientation and memory in rats, by employing the T-maze test. In the present work four new, tyrosine containing HN-derivatives were synthesized (Y-PAGASRLLLTGEIDLP, peptide I; Y-PAGASRLLLLTGEIDLP, peptide II; Y-SALLRSIPAPAGASRLLLTGEIDLP, peptide III; Y-SALLRSIPAPAGASRLLLLTGEIDLP, peptide IV). The neuroprotective action of these peptides was evaluated in the T-maze test and the most active among them (peptides I and III) was radiolabeled with (125)I. The pure monoradioiodinated peptides were used in: (i) in vitro binding studies with various neuronal cell lines and with brain and stomach membranes from rats and mice and (ii) in vivo biodistribution studies in rats and mice. Moreover, the metabolic stability of the above radiolabeled peptides was studied. Under the experimental conditions used, our data do not confirm the existence of specific binding sites for HN on the neuronal tissue. Nevertheless, they are setting the basis for further relevant studies aiming at the clarification of the mode of the neuroprotective action of HN-peptides.
authors: Institute of Radioisotopes and Radiodiagnostic Products, NCSR Demokritos, 153 10 Athens, Greece.
authors: Alexandra
authors: A
authors: Evangelou
authors: Christos
authors: C
authors: Zikos
authors: Dimitra
authors: D
authors: Benaki
authors: Maria
authors: M
authors: Pelecanou
authors: Penelope
authors: P
authors: Bouziotis
authors: Minas
authors: M
authors: Papadopoulos
authors: Lenka
authors: L
authors: Borovickova
authors: Iva
authors: I
authors: Vesela
authors: Tomas
authors: T
authors: Elbert
authors: Gabriela
authors: G
authors: Kunesová
authors: Ioannis
authors: I
authors: Pirmettis
authors: Maria
authors: M
authors: Paravatou-Petsotas
authors: Jirina
authors: J
authors: Slaninová
authors: Evangelia
authors: E
authors: Livaniou
mesh_terms: D000818:Animals; D002460:Cell Line; D002855:Chromatography, Thin Layer; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000737:chemistry*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007457:Iodine Radioisotopes; D018696:Neuroprotective Agents; C427211:humanin