title: Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant-induced cell death.
abstract: Atherosclerotic plaque destabilization is the major determinant of most acute coronary events. Smooth muscle cell (SMC) death contributes to plaque destabilization. Here, we describe a novel antiapoptotic mechanism in vascular SMCs that involves interaction of nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with apurinic/apyrimidinic endonuclease 1 (Ape1), the major oxidized DNA repair enzyme. GAPDH down-regulation potentiated H2O2-induced DNA damage and SMC apoptosis. Conversely, GAPDH overexpression decreased DNA damage and protected SMCs against apoptosis. Ape1 down-regulation reversed the resistance of GAPDH-overexpressing cells to DNA damage and apoptosis, which indicated that Ape1 is indispensable for GAPDH-dependent protective effects. GAPDH bound Ape1 in the SMC nucleus, and blocking (or oxidation) of GAPDH active site cysteines suppressed GAPDH/Ape1 interaction and potentiated apoptosis. GAPDH up-regulated Ape1viaa transcription factor homeobox protein Hox-A5-dependent mechanism. GAPDH levels were reduced in atherosclerotic plaque SMCs, and this effect correlated with oxidative stress and SMC apoptosis. Thus, we demonstrated that nuclear GAPDH/Ape1 interaction preserved Ape1 activity, reduced DNA damage, and prevented SMC apoptosis. Suppression of SMC apoptosis by maintenance of nuclear GAPDH/Ape1 interactions may be a novel therapy to increase atherosclerotic plaque stability.-Hou, X., Snarski, P., Higashi, Y., Yoshida, T., Jurkevich, A., Delafontaine, P., Sukhanov, S. Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant-induced cell death.
authors.affiliation: Department of Medicine, School of Medicine, University of Missouri at Columbia, Columbia, Missouri, USA.
authors.forename: Xuwei
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Medicine, School of Medicine, University of Missouri at Columbia, Columbia, Missouri, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Snarski
authors.affiliation: Department of Medicine, School of Medicine, University of Missouri at Columbia, Columbia, Missouri, USA.|Department of Physiology and Medical Pharmacology, School of Medicine, University of Missouri at Columbia, Columbia, Missouri, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Higashi
authors.affiliation: Department of Medicine, School of Medicine, University of Missouri at Columbia, Columbia, Missouri, USA.|Department of Physiology and Medical Pharmacology, School of Medicine, University of Missouri at Columbia, Columbia, Missouri, USA.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Molecular Cytology Core, University of Missouri at Columbia, Columbia, Missouri, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jurkevich
authors.affiliation: Department of Medicine, School of Medicine, University of Missouri at Columbia, Columbia, Missouri, USA.|Department of Physiology and Medical Pharmacology, School of Medicine, University of Missouri at Columbia, Columbia, Missouri, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Delafontaine
authors.affiliation: Department of Medicine, School of Medicine, University of Missouri at Columbia, Columbia, Missouri, USA; sukhanovs@health.missouri.edu.|Department of Physiology and Medical Pharmacology, School of Medicine, University of Missouri at Columbia, Columbia, Missouri, USA.
authors.forename: Sergiy
authors.initials: S
authors.lastname: Sukhanov
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002467:Cell Nucleus / Q000201:enzymology; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism*; D006861:Hydrogen Peroxide; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats
chemical_list: D001057:Apolipoproteins E; D006861:Hydrogen Peroxide; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); C486216:Apex1 protein, mouse; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: GAPDH; apoptosis; oxidative stress