title: Induction of endoplasmic reticulum stress and the modulation of thioredoxin-1 in formaldehyde-induced neurotoxicity.
abstract: Formaldehyde (FA), a common environmental pollutant, has toxic effects on central nervous system. The detailed mechanisms on FA-induced neurotoxicity have not been fully elucidated. In this study, we found that glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) expression, biomarkers of endoplasmic reticulum (ER) stress, were increased and pro-caspase-12 was decreased after PC12 cells exposure to FA. These results suggest that FA actually induces ER stress. Thioredoxin-1 (Trx-1) has various biological activities, including the control of redox balance, the modulation of ER stress and inhibition of apoptosis. In the present study, Trx-1 expression was increased at early stage, but decreased at late stage after FA treatment. Knockdown of Trx-1 expression increased the susceptibility of PC12 cells to FA-induced neurotoxicity. We also found that ginsenoside Rg1 had the potential to induce Trx-1 expression and attenuated neurotoxicity induced by FA. ER stress caused by FA was suppressed by ginsenoside Rg1. These data indicate that Trx-1 is a therapeutic candidate for protecting against FA-induced neurotoxicity.
authors.affiliation: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
authors.forename: Fu-Cheng
authors.initials: FC
authors.lastname: Luo
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Lv
authors.forename: Lei
authors.initials: L
authors.lastname: Qi
authors.forename: Sheng-Dong
authors.initials: SD
authors.lastname: Wang
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
mesh_terms: D000818:Animals; D053454:Caspase 12 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D005557:Formaldehyde / Q000633:toxicity*; D005786:Gene Expression Regulation; D036145:Ginsenosides / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016716:PC12 Cells; D034622:RNA Interference; D051381:Rats; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism; D014162:Transfection
chemical_list: C497251:Ddit3 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; D004785:Environmental Pollutants; C051684:GRP78 protein, rat; D036145:Ginsenosides; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018696:Neuroprotective Agents; C515559:Txn1 protein, mouse; D051742:Transcription Factor CHOP; D005557:Formaldehyde; D013879:Thioredoxins; C506440:Casp12 protein, mouse; D053454:Caspase 12; C035054:ginsenoside Rg1