title: Inhibition of ALDH2 protects PC12 cells against formaldehyde-induced cytotoxicity: involving the protection of hydrogen sulphide.
abstract: Formaldehyde (FA), a common environmental contaminant, has toxic effects on the central nervous system (CNS). We have previously found that hydrogen sulphide (H2S), the third endogenous gaseous mediator, protects neuron against the toxicity of FA. However, the underlying mechanism is poor. Aldehyde-dehydrogenase-2 (ALDH2) plays a major role in detoxification of reactive aldehyde in a range of organs and cell types. Therefore, we speculated that H2S antagonizes FA-induced neurotoxicity by modulating ALDH2. In the present study, we found that the exposure of PC12 cells to FA causes increase in ALDH2 expression and activity. Daidzin, an inhibitor of ALDH2, significantly antagonizes FA-exerted cytotoxicity and oxidative stress including the accumulation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-trans-nonenal (4-HNE), and malondialdehyde (MDA), in PC12 cells. We also showed that daidzin markedly attenuated FA-induced apoptosis in PC12 cells. Furthermore, we found that H2S reverses FA-elicited upregulation of ALDH2 in PC12 cells. Our results demonstrated the involvement of downregulation of ALDH2 in the protection of H2S against FA neurotoxicity.
authors.affiliation: Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan, China.|Institute of Neuroscience, Medical College, University of South China, Hengyang, Hunan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang, Hunan, China.
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Zhou
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang, Hunan, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan, China.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Huang
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, Hunan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang, Hunan, China.
authors.forename: Hong-Feng
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan, China.|Institute of Neuroscience, Medical College, University of South China, Hengyang, Hunan, China.
authors.forename: Xiao-Qing
authors.identifier: http://orcid.org/0000-0002-3518-9275
authors.initials: XQ
authors.lastname: Tang
mesh_terms: D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D003603:Cytotoxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
chemical_list: D003603:Cytotoxins; D005557:Formaldehyde; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; D006862:Hydrogen Sulfide
keywords: PC12 cells; aldehyde-dehydrogenase-2; formaldehyde; hydrogen sulphide; neurotoxicity