title: Down-regulation of aldose reductase renders J774A.1 cells more susceptible to acrolein- or hydrogen peroxide-induced cell death.
abstract: Aldose reductase (AR) is abundantly expressed in a variety of cell lineages and has been implicated in the cellular response against oxidative stress. However, the exact functional role of AR against oxidative stress remains relatively unclear. This study investigated the role of AR in acrolein- or hydrogen peroxide-induced apoptosis using the J774.A.1 macrophage cell line. Ablation of AR with a small interference RNA or inhibition of AR activity significantly enhanced the acrolein- or hydrogen peroxide-induced generation of reactive oxygen species and aldehydes, leading to increased apoptotic cell death. Blockade of AR activity in J774A.1 cells markedly augmented the acrolein- or hydrogen peroxide-induced translocation of Bax to mitochondria along with reduced Bcl-2 and increased release of cytochrome c from the mitochodria. Taken together, these findings indicate that AR plays an important role in the cellular response against oxidative stress, by sequestering the reactive molecules generated in cells exposed to toxic substances.
authors.affiliation: Department of Pharmacology, Gyeongsang Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Korea.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Kang
authors.forename: Gil Hyeong
authors.initials: GH
authors.lastname: Kim
authors.forename: Im Sun
authors.initials: IS
authors.lastname: Woo
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: So Young
authors.initials: SY
authors.lastname: Eun
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Ham
authors.forename: Hana
authors.initials: H
authors.lastname: Jin
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Park
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.forename: Jae Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yabe-Nishimura
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
mesh_terms: D000171:Acrolein / Q000494:pharmacology*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005949:Glucose Oxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000447:Aldehydes; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D000171:Acrolein; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D000449:Aldehyde Reductase; D005949:Glucose Oxidase