title: Effects of formaldehyde on mitochondrial dysfunction and apoptosis in SK-N-SH neuroblastoma cells.
abstract: Methanol ingestion is neurotoxic in humans due to its metabolites, formaldehyde and formic acid. Here, we compared the cytotoxicity of methanol and its metabolites on different types of cells. While methanol and formic acid did not affect the viability of the cells, formaldehyde (200-800 μg/mL) was strongly cytotoxic in all cell types tested. We investigated the effects of formaldehyde on oxidative stress, mitochondrial respiratory functions, and apoptosis on the sensitive neuronal SK-N-SH cells. Oxidative stress was induced after 2 h of formaldehyde exposure. Formaldehyde at a concentration of 400 μg/mL for 12 h of treatment greatly reduced cellular adenosine triphosphate (ATP) levels. Confocal microscopy indicated that the mitochondrial membrane potential (MMP) was dose-dependently reduced by formaldehyde. A marked and dose-dependent inhibition of mitochondrial respiratory enzymes, viz., NADH dehydrogenase (complex I), cytochrome c oxidase (complex IV), and oxidative stress-sensitive aconitase was also detected following treatment with formaldehyde. Furthermore, formaldehyde caused a concentration-dependent increase in nuclear fragmentation and in the activities of the apoptosis-initiator caspase-9 and apoptosis-effector caspase-3/-7, indicating apoptosis progression. Our data suggests that formaldehyde exerts strong cytotoxicity, at least in part, by inducing oxidative stress, mitochondrial dysfunction, and eventually apoptosis. Changes in mitochondrial respiratory function and oxidative stress by formaldehyde may therefore be critical in methanol-induced toxicity.
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan, Chungnam, 330-090, South Korea.
authors.forename: Tamanna
authors.initials: T
authors.lastname: Zerin
authors.affiliation: Pesticide Poisoning center, Soonchunhyang University Cheonan Hospital, Cheonan, South Korea.
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Pesticide Poisoning center, Soonchunhyang University Cheonan Hospital, Cheonan, South Korea.
authors.forename: Hyo-Wook
authors.initials: HW
authors.lastname: Gil
authors.affiliation: Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan, Chungnam, 330-090, South Korea. songmic@sch.ac.kr.
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
authors.affiliation: Pesticide Poisoning center, Soonchunhyang University Cheonan Hospital, Cheonan, South Korea. syhong@sch.ac.kr.|Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, 23-20, Bongmyung-Dong, Cheonan, 330-721, South Korea. syhong@sch.ac.kr.
authors.forename: Sae-Yong
authors.initials: SY
authors.lastname: Hong
mesh_terms: D000154:Aconitate Hydratase / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005557:Formaldehyde / Q000633:toxicity*; D005561:Formates / Q000633:toxicity*; D005786:Gene Expression Regulation; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D000432:Methanol / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress; D015398:Signal Transduction
chemical_list: D005561:Formates; D009498:Neurotoxins; C030544:formic acid; D005557:Formaldehyde; D000255:Adenosine Triphosphate; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; C505407:CASP3 protein, human; C505520:CASP7 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9; D000154:Aconitate Hydratase; D000432:Methanol
keywords: Caspase-3/-7; Caspase-9; Formaldehyde; Mitochondrial membrane potential; Mitochondrial respiratory enzyme; Oxidative stress