In vitro study of ochratoxin A in the expression of genes associated with neuron survival and viability

Riddhi Sharma; Sean M. Gettings; Gareth Hazell; Nora Bourbia

doi:10.1016/j.tox.2022.153376

In vitro study of ochratoxin A in the expression of genes associated with neuron survival and viability

Riddhi Sharma, Sean M. Gettings, Gareth Hazell, Nora Bourbia^*

^*Corresponding author for this work

Radiation Effects

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

32 Downloads (Pure)

Abstract

Ochratoxin A (OTA) is a common mycotoxin and known contaminant of crops, foods and drinks. As OTA crosses the blood-brain barrier, this study investigated the role of OTA, as an environmental hazard, on neuronal survival and viability. The impact of a range of OTA concentrations on the expression of MAPT, BAX, P53, BDNF and TPPP genes was investigated using human neuroblastoma (SH-SY5Y) cells. The absence of altered gene expression determined using reverse transcription quantitative PCR demonstrated that exposure to a typical daily dose of OTA delivered to the brain (2 fM), may not trigger neuronal dysfunction. However, a dose of OTA (2 pM) decreased BDNF expression. BDNF and TPPP expression were significantly reduced after 1 day and significantly increased after 2 days of exposure to 1 µM OTA. The expression of P53, MAPT, and BAX was reduced at both days. Thus, despite OTA cytotoxicity, SH-SY5Y cells entered a survival state following a strong toxic insult. A typical daily environmental OTA exposure does not appear to carry an increased risk of neurodegenerative disease. However, BDNF dysfunction may occur through prolonged exposure to a dose one thousand times higher than the typical daily consumed OTA dose potentially causing adverse effects on neuronal health.

Original language	English
Article number	153376
Journal	Toxicology
Volume	483
Early online date	15 Nov 2022
DOIs	https://doi.org/10.1016/j.tox.2022.153376
Publication status	Published - 1 Jan 2023

Bibliographical note

Funding Information: This study is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Chemical and Radiation Threats and Hazards, a partnership between UK Health Security Agency and Imperial College London ( NIHR200922 ). The views expressed are those of the author(s) and not necessarily those of the NIHR, UK Health Security Agency or the Department of Health and Social Care.

Open Access: . This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Publisher Copyright: Crown Copyright © 2022 Published by Elsevier B.V

Citation: Riddhi Sharma, Sean M. Gettings, Gareth Hazell, Nora Bourbia,
In vitro study of ochratoxin A in the expression of genes associated with neuron survival and viability, Toxicology, Volume 483, 2023, 153376, ISSN 0300-483X,
https://doi.org/10.1016/j.tox.2022.153376.

DOI: https://doi.org/10.1016/j.tox.2022.153376

Keywords

BDNF
Mycotoxin
Neuron
Ochratoxin A
SH-SY5Y
Survival

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.tox.2022.153376Licence: CC BY

Sharma2023InVitroStudyOfOchratoxinAInTheExpressionOfGenesAssociatedWithNeuronSurvivalAndViabilityToxicologyFinal published version, 4.19 MBLicence: CC BY

Cite this

@article{db8177962cbd479783789321b47767eb,

title = "In vitro study of ochratoxin A in the expression of genes associated with neuron survival and viability",

abstract = "Ochratoxin A (OTA) is a common mycotoxin and known contaminant of crops, foods and drinks. As OTA crosses the blood-brain barrier, this study investigated the role of OTA, as an environmental hazard, on neuronal survival and viability. The impact of a range of OTA concentrations on the expression of MAPT, BAX, P53, BDNF and TPPP genes was investigated using human neuroblastoma (SH-SY5Y) cells. The absence of altered gene expression determined using reverse transcription quantitative PCR demonstrated that exposure to a typical daily dose of OTA delivered to the brain (2 fM), may not trigger neuronal dysfunction. However, a dose of OTA (2 pM) decreased BDNF expression. BDNF and TPPP expression were significantly reduced after 1 day and significantly increased after 2 days of exposure to 1 µM OTA. The expression of P53, MAPT, and BAX was reduced at both days. Thus, despite OTA cytotoxicity, SH-SY5Y cells entered a survival state following a strong toxic insult. A typical daily environmental OTA exposure does not appear to carry an increased risk of neurodegenerative disease. However, BDNF dysfunction may occur through prolonged exposure to a dose one thousand times higher than the typical daily consumed OTA dose potentially causing adverse effects on neuronal health.",

keywords = "BDNF, Mycotoxin, Neuron, Ochratoxin A, SH-SY5Y, Survival",

author = "Riddhi Sharma and Gettings, {Sean M.} and Gareth Hazell and Nora Bourbia",

note = "Funding Information: This study is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Chemical and Radiation Threats and Hazards, a partnership between UK Health Security Agency and Imperial College London ( NIHR200922 ). The views expressed are those of the author(s) and not necessarily those of the NIHR, UK Health Security Agency or the Department of Health and Social Care. Open Access: . This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Publisher Copyright: Crown Copyright {\textcopyright} 2022 Published by Elsevier B.V Citation: Riddhi Sharma, Sean M. Gettings, Gareth Hazell, Nora Bourbia, In vitro study of ochratoxin A in the expression of genes associated with neuron survival and viability, Toxicology, Volume 483, 2023, 153376, ISSN 0300-483X, https://doi.org/10.1016/j.tox.2022.153376. DOI: https://doi.org/10.1016/j.tox.2022.153376",

year = "2023",

month = jan,

day = "1",

doi = "10.1016/j.tox.2022.153376",

language = "English",

volume = "483",

journal = "Toxicology",

issn = "0300-483X",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - In vitro study of ochratoxin A in the expression of genes associated with neuron survival and viability

AU - Sharma, Riddhi

AU - Gettings, Sean M.

AU - Hazell, Gareth

AU - Bourbia, Nora

N1 - Funding Information: This study is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Chemical and Radiation Threats and Hazards, a partnership between UK Health Security Agency and Imperial College London ( NIHR200922 ). The views expressed are those of the author(s) and not necessarily those of the NIHR, UK Health Security Agency or the Department of Health and Social Care. Open Access: . This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Publisher Copyright: Crown Copyright © 2022 Published by Elsevier B.V Citation: Riddhi Sharma, Sean M. Gettings, Gareth Hazell, Nora Bourbia, In vitro study of ochratoxin A in the expression of genes associated with neuron survival and viability, Toxicology, Volume 483, 2023, 153376, ISSN 0300-483X, https://doi.org/10.1016/j.tox.2022.153376. DOI: https://doi.org/10.1016/j.tox.2022.153376

PY - 2023/1/1

Y1 - 2023/1/1

N2 - Ochratoxin A (OTA) is a common mycotoxin and known contaminant of crops, foods and drinks. As OTA crosses the blood-brain barrier, this study investigated the role of OTA, as an environmental hazard, on neuronal survival and viability. The impact of a range of OTA concentrations on the expression of MAPT, BAX, P53, BDNF and TPPP genes was investigated using human neuroblastoma (SH-SY5Y) cells. The absence of altered gene expression determined using reverse transcription quantitative PCR demonstrated that exposure to a typical daily dose of OTA delivered to the brain (2 fM), may not trigger neuronal dysfunction. However, a dose of OTA (2 pM) decreased BDNF expression. BDNF and TPPP expression were significantly reduced after 1 day and significantly increased after 2 days of exposure to 1 µM OTA. The expression of P53, MAPT, and BAX was reduced at both days. Thus, despite OTA cytotoxicity, SH-SY5Y cells entered a survival state following a strong toxic insult. A typical daily environmental OTA exposure does not appear to carry an increased risk of neurodegenerative disease. However, BDNF dysfunction may occur through prolonged exposure to a dose one thousand times higher than the typical daily consumed OTA dose potentially causing adverse effects on neuronal health.

AB - Ochratoxin A (OTA) is a common mycotoxin and known contaminant of crops, foods and drinks. As OTA crosses the blood-brain barrier, this study investigated the role of OTA, as an environmental hazard, on neuronal survival and viability. The impact of a range of OTA concentrations on the expression of MAPT, BAX, P53, BDNF and TPPP genes was investigated using human neuroblastoma (SH-SY5Y) cells. The absence of altered gene expression determined using reverse transcription quantitative PCR demonstrated that exposure to a typical daily dose of OTA delivered to the brain (2 fM), may not trigger neuronal dysfunction. However, a dose of OTA (2 pM) decreased BDNF expression. BDNF and TPPP expression were significantly reduced after 1 day and significantly increased after 2 days of exposure to 1 µM OTA. The expression of P53, MAPT, and BAX was reduced at both days. Thus, despite OTA cytotoxicity, SH-SY5Y cells entered a survival state following a strong toxic insult. A typical daily environmental OTA exposure does not appear to carry an increased risk of neurodegenerative disease. However, BDNF dysfunction may occur through prolonged exposure to a dose one thousand times higher than the typical daily consumed OTA dose potentially causing adverse effects on neuronal health.

KW - BDNF

KW - Mycotoxin

KW - Neuron

KW - Ochratoxin A

KW - SH-SY5Y

KW - Survival

UR - http://www.scopus.com/inward/record.url?scp=85142178172&partnerID=8YFLogxK

U2 - 10.1016/j.tox.2022.153376

DO - 10.1016/j.tox.2022.153376

M3 - Article

AN - SCOPUS:85142178172

SN - 0300-483X

VL - 483

JO - Toxicology

JF - Toxicology

M1 - 153376

ER -

In vitro study of ochratoxin A in the expression of genes associated with neuron survival and viability

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this