title: Propyl gallate is a superoxide dismutase mimic and protects cultured lens epithelial cells from H2O2 insult.
abstract: n-Propyl gallate (nPG) is a food preservative that is generally regarded as safe by the US FDA. It suppresses oxidation in biological systems. The mechanism by which nPG acts in biological systems is uncertain. We investigated whether nPG protected cultured lens epithelial cells from H(2)O(2)-induced damage. Cells were treated with H(2)O(2) or with nPG and then H(2)O(2). H(2)O(2) inhibited growth, caused membrane blebbing, decreased lactate production, increased the level of GSSG, decreased the levels of GSH, ATP and NAD(+), and G3PDH activity, stimulated the hexose monophosphate shunt and induced single-strand breaks in DNA. nPG prevented the H(2)O(2)-induced growth inhibition, membrane blebbing, drop in NAD(+) and single-strand breaks in DNA. The mechanism by which nPG acts at the chemical level was investigated using electron paramagnetic resonance (EPR), direct spectrophotometric kinetic measurements, and cyclic voltammetry. When nPG at low concentrations (nM to microM) was mixed with a large excess of O(2)(-)*, the superoxide signal was destroyed as indicated by UV visible spectroscopy and EPR. Kinetic analysis indicated that nPG dismutated O(2)(-)* in repetitive additions of superoxide with little loss of activity. The rate constant for the overall reaction of nPG with O(2)(-)* was ca. 10(6)M(-1)s(-1). nPG had a very low specific binding constant for Fe(2+) as determined by cyclic voltammetry. The evidence indicates that nPG dismutates the superoxide ion in a catalytic manner.
authors.affiliation: Department of Biological Sciences, Oakland University, Rochester, MI 48039, USA. reddan@oakland.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Reddan
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Giblin
authors.forename: Michael
authors.initials: M
authors.lastname: Sevilla
authors.forename: Vanita
authors.initials: V
authors.lastname: Padgaonkar
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Dziedzic
authors.forename: Victor R
authors.initials: VR
authors.lastname: Leverenz
authors.forename: Indira C
authors.initials: IC
authors.lastname: Misra
authors.forename: Justin S
authors.initials: JS
authors.lastname: Chang
authors.forename: John T
authors.initials: JT
authors.lastname: Pena
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011435:Propyl Gallate / Q000494:pharmacology*; D011817:Rabbits; D013482:Superoxide Dismutase / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D013481:Superoxides; D011435:Propyl Gallate; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase