Heme oxygenase-1 induction by dieldrin in dopaminergic cells.
We investigated the transcriptional events and signaling pathways involved in the induction of heme oxygenase-1 (HO-1) by dieldrin, an environmental risk factor of Parkinson's disease, in a dopaminergic neuronal cells (SN4741). Dieldrin exposure caused dose-dependent and time-dependent induction of heme oxygenase activity and HO-1 protein expression. Deletional and mutational analyses showed that the 5' distal enhancers, E1 and E2, mediate dieldrin-induced HO-1 gene transcription, and the AP-1 DNA binding sites in the E2 enhancer are critical for E2-mediated HO-1 gene activation. Furthermore, both the p38 and JNK mitogen-activated protein kinase pathways are utilized for HO-1 transcriptional activation by dieldrin. HO-1 inhibitor, ZnPP IX reduced the expression of HO-1 but enhanced the cytotoxicity induced by dieldrin.
Kim
Do Kyung
DK
Department of Oral Physiology, Chosun University College of Dentistry, Chosun University, 375 Seosuk-dong, Gwangju 501-759, Republic of Korea.
Kim
Jae-Sung
JS
Kim
Ji-Eun
JE
Kim
Sung-Jun
SJ
Lee
Jung-Sup
JS
Kim
Dae-Joong
DJ
Son
Jin H
JH
Chun
Hong Sung
HS
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004026:Dieldrin / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D008565:Membrane Proteins; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016296:Mutagenesis / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D015533:Transcriptional Activation; D014162:Transfection / Q000379:methods; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008565:Membrane Proteins; D008156:Luciferases; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D004026:Dieldrin; D004298:Dopamine