Evaluation of toxicological monitoring markers using proteomic analysis in rats exposed to formaldehyde

Hosub Im, Eunha Oh, Joohee Mun, Jin Young Khim, Eun Il Lee, Hyung Sik Kang, Eunmi Kim, Hyunsuk Kim, Nam Hee Won, Young Hwan Kim, Woon Won Jung, Dong Geun Sul

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Formaldehyde (FA) is known as a low molecule weight organic compound and one of major components that causes sick building syndrome (SBS), and it has been reported that FA has cytotoxic, hemotoxic, immunotoxic, and genotoxic properties. The International Agency for Research on Cancer (IARC) has characterized FA as a carcinogen. In this study, we investigated the effects of FA on rat plasma proteins by using proteomic approach. Rats were exposed to three different concentrations of FA (0, 5, 10 ppm) for 2 weeks at 6 hours/day and 5 days/week in an inhalation chamber. Malondialdehyde (MDA) assay and carbonyl spectrometric assay were conducted to determine lipid peroxidation and protein oxidation levels and Comet assays were used for genotoxicity evaluation. Level of MDA, carbonyl insertion and DNA damage in plasma, livers, and in the lymphocytes of rats exposed to FA were found to be dose dependently increased. Proteomic analysis using three different pl ranges (3.5-5.6, 5.3-6.9, 6-9) and large size two-dimensional gel electrophoresis (2-DE) showed the presence of 3491 protein spots. A total of 32 (19 up- and 13 down-regulated) proteins were identified as biomarkers of FA, all showed dose dependent expressions in the plasma of rats exposed to FA and of these, 27 protein spots were identified by MALDI-TOF/MS. Several differentiated protein groups were found. Proteins involved in apoptosis, transportation, signaling, energy metabolism, and cell structure and motility were found to be up- or down-regulated. Among these, the identities of SNAP 23, apolipoprotein A-1 and E, clusterin, kinesin, and fibrinogen γ were confirmed by Western blot assay, and apo E was further analyzed by using 2-DE immunoblot assays to determine isoform patterns. Two cytokine including IL4 and INF-γ were measured in plasma with respect to fibrinogen γ changes, in summary, cytotoxicity, and genotoxicity assays, namely MDA lipid peroxidation assay, the carbonyl protein oxidation assay, and Comet genotoxic assay showed that these effects increased on increasing FA levels. Proteomic analysis with three different pl ranges and long size 2-DE gel electrophoresis showed that 32 protein spots were up-or down-regulated. Of these 32 proteins, 7 proteins were confirmed by western blot assay. They could be potential biomarkers for human diseases associated with FA exposure.

Original languageEnglish
Pages (from-to)1354-1366
Number of pages13
JournalJournal of Proteome Research
Volume5
Issue number6
DOIs
Publication statusPublished - 2006 Jun 1

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Proteomics
Toxicology
Formaldehyde
Rats
Assays
Monitoring
Proteins
Malondialdehyde
Comet Assay
Apolipoproteins E
Biomarkers
Electrophoresis
Plasmas
Fibrinogen
Lipid Peroxidation
Sick Building Syndrome
Western Blotting
Gels
Clusterin
International Agencies

Keywords

  • Apolipoprotein A-1
  • Apolipoprotein E
  • Formaldehyde
  • Matrix-assisted laser desorption/ionization- time-of-flight mass spectrometry
  • Proteomics
  • Rat plasma
  • Sick building syndrome
  • Two-dimensional polyacrylamide gel electrophoresis

ASJC Scopus subject areas

  • Genetics
  • Biotechnology
  • Biochemistry

Cite this

Evaluation of toxicological monitoring markers using proteomic analysis in rats exposed to formaldehyde. / Im, Hosub; Oh, Eunha; Mun, Joohee; Khim, Jin Young; Lee, Eun Il; Kang, Hyung Sik; Kim, Eunmi; Kim, Hyunsuk; Won, Nam Hee; Kim, Young Hwan; Jung, Woon Won; Sul, Dong Geun.

In: Journal of Proteome Research, Vol. 5, No. 6, 01.06.2006, p. 1354-1366.

Research output: Contribution to journalArticle

Im, H, Oh, E, Mun, J, Khim, JY, Lee, EI, Kang, HS, Kim, E, Kim, H, Won, NH, Kim, YH, Jung, WW & Sul, DG 2006, 'Evaluation of toxicological monitoring markers using proteomic analysis in rats exposed to formaldehyde', Journal of Proteome Research, vol. 5, no. 6, pp. 1354-1366. https://doi.org/10.1021/pr050437b
Im, Hosub ; Oh, Eunha ; Mun, Joohee ; Khim, Jin Young ; Lee, Eun Il ; Kang, Hyung Sik ; Kim, Eunmi ; Kim, Hyunsuk ; Won, Nam Hee ; Kim, Young Hwan ; Jung, Woon Won ; Sul, Dong Geun. / Evaluation of toxicological monitoring markers using proteomic analysis in rats exposed to formaldehyde. In: Journal of Proteome Research. 2006 ; Vol. 5, No. 6. pp. 1354-1366.
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AU - Im, Hosub

AU - Oh, Eunha

AU - Mun, Joohee

AU - Khim, Jin Young

AU - Lee, Eun Il

AU - Kang, Hyung Sik

AU - Kim, Eunmi

AU - Kim, Hyunsuk

AU - Won, Nam Hee

AU - Kim, Young Hwan

AU - Jung, Woon Won

AU - Sul, Dong Geun

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N2 - Formaldehyde (FA) is known as a low molecule weight organic compound and one of major components that causes sick building syndrome (SBS), and it has been reported that FA has cytotoxic, hemotoxic, immunotoxic, and genotoxic properties. The International Agency for Research on Cancer (IARC) has characterized FA as a carcinogen. In this study, we investigated the effects of FA on rat plasma proteins by using proteomic approach. Rats were exposed to three different concentrations of FA (0, 5, 10 ppm) for 2 weeks at 6 hours/day and 5 days/week in an inhalation chamber. Malondialdehyde (MDA) assay and carbonyl spectrometric assay were conducted to determine lipid peroxidation and protein oxidation levels and Comet assays were used for genotoxicity evaluation. Level of MDA, carbonyl insertion and DNA damage in plasma, livers, and in the lymphocytes of rats exposed to FA were found to be dose dependently increased. Proteomic analysis using three different pl ranges (3.5-5.6, 5.3-6.9, 6-9) and large size two-dimensional gel electrophoresis (2-DE) showed the presence of 3491 protein spots. A total of 32 (19 up- and 13 down-regulated) proteins were identified as biomarkers of FA, all showed dose dependent expressions in the plasma of rats exposed to FA and of these, 27 protein spots were identified by MALDI-TOF/MS. Several differentiated protein groups were found. Proteins involved in apoptosis, transportation, signaling, energy metabolism, and cell structure and motility were found to be up- or down-regulated. Among these, the identities of SNAP 23, apolipoprotein A-1 and E, clusterin, kinesin, and fibrinogen γ were confirmed by Western blot assay, and apo E was further analyzed by using 2-DE immunoblot assays to determine isoform patterns. Two cytokine including IL4 and INF-γ were measured in plasma with respect to fibrinogen γ changes, in summary, cytotoxicity, and genotoxicity assays, namely MDA lipid peroxidation assay, the carbonyl protein oxidation assay, and Comet genotoxic assay showed that these effects increased on increasing FA levels. Proteomic analysis with three different pl ranges and long size 2-DE gel electrophoresis showed that 32 protein spots were up-or down-regulated. Of these 32 proteins, 7 proteins were confirmed by western blot assay. They could be potential biomarkers for human diseases associated with FA exposure.

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KW - Matrix-assisted laser desorption/ionization- time-of-flight mass spectrometry

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KW - Rat plasma

KW - Sick building syndrome

KW - Two-dimensional polyacrylamide gel electrophoresis

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