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Cell Biology and Toxicology

, Volume 31, Issue 6, pp 261–272 | Cite as

Effects of formaldehyde on mitochondrial dysfunction and apoptosis in SK-N-SH neuroblastoma cells

  • Tamanna Zerin
  • Jin-Sun Kim
  • Hyo-Wook Gil
  • Ho-Yeon SongEmail author
  • Sae-Yong HongEmail author
Original Article

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.

Keywords

Caspase-9 Caspase-3/-7 Formaldehyde Mitochondrial membrane potential Mitochondrial respiratory enzyme Oxidative stress 

Abbreviations

ADH

alcohol dehydrogenase

ATP

adenosine triphosphate

FACS

fluorescence-activated cell sorting

FBS

fetal bovine serum

FITC

fluorescein isothiocyanate

HBSS

Hanks balanced salt solution

MMP

mitochondrial membrane potential

PBS

phosphate-buffered saline

ROS

reactive oxygen species

Notes

Acknowledgements

This work was carried out with the support of “the Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ2015)”, Rural Development Administration, South Korea.

Compliance with ethical standard

Conflict of interest

The authors declare that there are no conflicts of interest.

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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Department of Microbiology, College of MedicineSoonchunhyang UniversityCheonanSouth Korea
  2. 2.Pesticide Poisoning centerSoonchunhyang University Cheonan HospitalCheonanSouth Korea
  3. 3.Department of Internal MedicineSoonchunhyang University Cheonan HospitalCheonanSouth Korea

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