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BDNF-TrkB Pathway Mediates Neuroprotection of Hydrogen Sulfide against Formaldehyde-Induced Toxicity to PC12 Cells

Formaldehyde (FA) is a common environmental contaminant that has toxic effects on the central nervous system (CNS). Our previous data demonstrated that hydrogen sulfide (H(2)S), the third endogenous gaseous mediator, has protective effects against FA-induced neurotoxicity. As is known to all, Brain-...

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Autores principales: Jiang, Jia-Mei, Zhou, Cheng-Fang, Gao, Sheng-Lan, Tian, Ying, Wang, Chun-Yan, Wang, Li, Gu, Hong-Feng, Tang, Xiao-Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352058/
https://www.ncbi.nlm.nih.gov/pubmed/25749582
http://dx.doi.org/10.1371/journal.pone.0119478
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author Jiang, Jia-Mei
Zhou, Cheng-Fang
Gao, Sheng-Lan
Tian, Ying
Wang, Chun-Yan
Wang, Li
Gu, Hong-Feng
Tang, Xiao-Qing
author_facet Jiang, Jia-Mei
Zhou, Cheng-Fang
Gao, Sheng-Lan
Tian, Ying
Wang, Chun-Yan
Wang, Li
Gu, Hong-Feng
Tang, Xiao-Qing
author_sort Jiang, Jia-Mei
collection PubMed
description Formaldehyde (FA) is a common environmental contaminant that has toxic effects on the central nervous system (CNS). Our previous data demonstrated that hydrogen sulfide (H(2)S), the third endogenous gaseous mediator, has protective effects against FA-induced neurotoxicity. As is known to all, Brain-derived neurotropic factor (BDNF), a member of the neurotrophin gene family, mediates its neuroprotective properties via various intracellular signaling pathways triggered by activating the tyrosine kinase receptor B (TrkB). Intriguingly, our previous data have illustrated the upregulatory role of H(2)S on BDNF protein expression in the hippocampus of rats. Therefore, in this study, we hypothesized that H(2)S provides neuroprotection against FA toxicity by regulating BDNF-TrkB pathway. In the present study, we found that NaHS, a donor of H(2)S, upregulated the level of BDNF protein in PC12 cells, and significantly rescued FA-induced downregulation of BDNF levels. Furthermore, we found that pretreatment of PC12 cells with K252a, an inhibitor of the BDNF receptor TrkB, markedly reversed the inhibition of NaHS on FA-induced cytotoxicity and ablated the protective effects of NaHS on FA-induced oxidative stress, including the accumulation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-trans-nonenal (4-HNE), and malondialdehyde (MDA). We also showed that K252a abolished the inhibition of NaHS on FA-induced apoptosis, as well as the activation of caspase-3 in PC12 cells. In addition, K252a reversed the protection of H(2)S against FA-induced downregulation of Bcl-2 protein expression and upregulation of Bax protein expression in PC12 cells. These data indicate that the BDNF-TrkB pathway mediates the neuroprotection of H(2)S against FA-induced cytotoxicity, oxidative stress and apoptosis in PC12 cells. These findings provide a novel mechanism underlying the protection of H(2)S against FA-induced neurotoxicity.
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spelling pubmed-43520582015-03-17 BDNF-TrkB Pathway Mediates Neuroprotection of Hydrogen Sulfide against Formaldehyde-Induced Toxicity to PC12 Cells Jiang, Jia-Mei Zhou, Cheng-Fang Gao, Sheng-Lan Tian, Ying Wang, Chun-Yan Wang, Li Gu, Hong-Feng Tang, Xiao-Qing PLoS One Research Article Formaldehyde (FA) is a common environmental contaminant that has toxic effects on the central nervous system (CNS). Our previous data demonstrated that hydrogen sulfide (H(2)S), the third endogenous gaseous mediator, has protective effects against FA-induced neurotoxicity. As is known to all, Brain-derived neurotropic factor (BDNF), a member of the neurotrophin gene family, mediates its neuroprotective properties via various intracellular signaling pathways triggered by activating the tyrosine kinase receptor B (TrkB). Intriguingly, our previous data have illustrated the upregulatory role of H(2)S on BDNF protein expression in the hippocampus of rats. Therefore, in this study, we hypothesized that H(2)S provides neuroprotection against FA toxicity by regulating BDNF-TrkB pathway. In the present study, we found that NaHS, a donor of H(2)S, upregulated the level of BDNF protein in PC12 cells, and significantly rescued FA-induced downregulation of BDNF levels. Furthermore, we found that pretreatment of PC12 cells with K252a, an inhibitor of the BDNF receptor TrkB, markedly reversed the inhibition of NaHS on FA-induced cytotoxicity and ablated the protective effects of NaHS on FA-induced oxidative stress, including the accumulation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-trans-nonenal (4-HNE), and malondialdehyde (MDA). We also showed that K252a abolished the inhibition of NaHS on FA-induced apoptosis, as well as the activation of caspase-3 in PC12 cells. In addition, K252a reversed the protection of H(2)S against FA-induced downregulation of Bcl-2 protein expression and upregulation of Bax protein expression in PC12 cells. These data indicate that the BDNF-TrkB pathway mediates the neuroprotection of H(2)S against FA-induced cytotoxicity, oxidative stress and apoptosis in PC12 cells. These findings provide a novel mechanism underlying the protection of H(2)S against FA-induced neurotoxicity. Public Library of Science 2015-03-06 /pmc/articles/PMC4352058/ /pubmed/25749582 http://dx.doi.org/10.1371/journal.pone.0119478 Text en © 2015 Jiang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jiang, Jia-Mei
Zhou, Cheng-Fang
Gao, Sheng-Lan
Tian, Ying
Wang, Chun-Yan
Wang, Li
Gu, Hong-Feng
Tang, Xiao-Qing
BDNF-TrkB Pathway Mediates Neuroprotection of Hydrogen Sulfide against Formaldehyde-Induced Toxicity to PC12 Cells
title BDNF-TrkB Pathway Mediates Neuroprotection of Hydrogen Sulfide against Formaldehyde-Induced Toxicity to PC12 Cells
title_full BDNF-TrkB Pathway Mediates Neuroprotection of Hydrogen Sulfide against Formaldehyde-Induced Toxicity to PC12 Cells
title_fullStr BDNF-TrkB Pathway Mediates Neuroprotection of Hydrogen Sulfide against Formaldehyde-Induced Toxicity to PC12 Cells
title_full_unstemmed BDNF-TrkB Pathway Mediates Neuroprotection of Hydrogen Sulfide against Formaldehyde-Induced Toxicity to PC12 Cells
title_short BDNF-TrkB Pathway Mediates Neuroprotection of Hydrogen Sulfide against Formaldehyde-Induced Toxicity to PC12 Cells
title_sort bdnf-trkb pathway mediates neuroprotection of hydrogen sulfide against formaldehyde-induced toxicity to pc12 cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352058/
https://www.ncbi.nlm.nih.gov/pubmed/25749582
http://dx.doi.org/10.1371/journal.pone.0119478
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