title: Nucleoside 5'-phosphorothioate derivatives as oxidative stress protectants in PC12 cells.
abstract: Iron-induced oxidative damage of mitochondria contributes to cellular death seen in neurodegenerative diseases, therefore, there is a demand for nontoxic, biocompatible, and effective Fe-ion chelators. We evaluated the chelation of Fe(II) by phosphate derivatives using ferrozine as an indicator. We studied the effect of phosphate derivatives on inhibiting Fe(II)-induced oxidative stress in PC12 cells, and metabolic stability in PC12 cells was evaluated. Nucleotides containing phosphorothioate moieties inhibited ROS formation better than natural nucleotides and were more metabolically stable in PC12 cells. Finally, we elucidated that these nucleotides activate the MAP-kinase pathway that contributes to protection of PC12 cells under oxidative stress.
authors.affiliation: Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Ortal
authors.initials: O
authors.lastname: Danino
authors.forename: Shlomo
authors.initials: S
authors.lastname: Grossman
authors.forename: Bilha
authors.initials: B
authors.lastname: Fischer
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005296:Ferrous Compounds / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D054735:Phosphorothioate Oligonucleotides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005296:Ferrous Compounds; D054735:Phosphorothioate Oligonucleotides; D017382:Reactive Oxygen Species