Iron enhancement of oxidative DNA damage and neuronal cell death induced by salsolinol.
A group of naturally occurring isoquinoline alkaloids have been detected in certain regions of mammalian brain. One such compound is salsolinol (SAL; 1-methyl-6, 7-dihydroxy-1,2,3,4-tetrahydroisoquinoline). This endogenous isoquinoline derivative has been considered to be implicated in the pathophysiology of chronic alcoholism and Parkinsonism. The present study deals with the DNA strand scission induced by SAL in the presence of iron. Incubation of phiX174 DNA with SAL and ferric ion led to conversion of the supercoiled DNA to open circular and linear forms, which was inhibited by the iron chelator deferoxamine, catalase, and scavengers of reactive oxygen species. SAL in combination with Fe(III) also produced 8-hydroxydeoxyguanosine in calf thymus DNA. Exposure of PC12 cells to SAL produced concentration-dependent reduction in viability, which was exacerbated by iron and ameliorated by deferoxamine.
Surh
Young-Joon
YJ
Laboratory of Biochemistry and Molecular Toxicology, College of Pharmacy, Seoul National University, South Korea. surh@plaza.snu.ac.kr
Jung
Youn-Joo
YJ
Jang
Jung-Hee
JH
Lee
Jeong-Sang
JS
Yoon
Hye-Ran
HR
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002417:Cattle; D016923:Cell Death; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004278:DNA, Superhelical; D003676:Deferoxamine / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D007501:Iron / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D007546:Isoquinolines / Q000009:adverse effects*; D009474:Neurons; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D013950:Thymus Gland / Q000166:cytology
D004278:DNA, Superhelical; D007502:Iron Chelating Agents; D007546:Isoquinolines; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; C036617:salsolinol; D007501:Iron; D003849:Deoxyguanosine; D003676:Deferoxamine