Down-regulation of aldose reductase renders J774A.1 cells more susceptible to acrolein- or hydrogen peroxide-induced cell death.
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.
Kang
Eun Sil
ES
Department of Pharmacology, Gyeongsang Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Korea.
Kim
Gil Hyeong
GH
Woo
Im Sun
IS
Kim
Hyo Jung
HJ
Eun
So Young
SY
Ham
Sun Ah
SA
Jin
Hana
H
Kim
Min Young
MY
Park
Myung Hyun
MH
Kim
Hye Jung
HJ
Chang
Ki Churl
KC
Lee
Jae Heun
JH
Kim
Jin-Hoi
JH
Yabe-Nishimura
Chihiro
C
Seo
Han Geuk
HG
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
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