Identification of potential serum biomarkers in mercury-treated mice using a glycoproteomic approach.
Mercury is a well-recognized health hazard and a deleterious environmental contaminant. Exposure to mercury can cause neurotoxic manifestations, nephrotoxicity, and immune function alterations; however, the mechanisms and related proteins responsible for these effects are still unclear. Our goal is to understand the relationship between the toxicity of mercury and the proteins affected by this toxic heavy metal and to define biomarkers for mercury intoxication. Two different forms of mercury, organic methylmercury or inorganic mercury sulfide, were orally administered to the mice for 4 weeks. To reduce complexity of the serum proteome, we enriched glycoproteins from mice serum with lectin concanavalin A resin, and the tryptic peptides of the purified glycoproteins were subjected to nanoultra performance liquid chromatography-Quadrupole time-of-flight for identification and label-free quantification. In this study, we characterized approximately 209 proteins from mice serum, and, among them, 21 proteins were differentially expressed in organic methylmercury-treated mice serum compared with the control group. Two proteins, serum amyloid P component (SAP) and inter α-trypsin inhibitor heavy chain 4 (ITI-H4), were upregulated in organic methylmercury-treated mice and confirmed with different doses of both types of mercury by Western blot analysis. Results of immunohistochemistry also confirmed the validity of SAP and ITI-H4 as biomarker candidates for organic methylmercury exposure. Findings of this study may assist in understanding the relationship between toxicity of mercury and upregulated proteins in mouse serum. Furthermore, the proteins identified here might be used as biomarker candidates in mercury intoxication.
School of Medicine, Kyungpook National University, 101 Dongin-dong 2 Ga, Jung-gu, Daegu 700-422, Republic of Korea. Email: mcbaek@knu.ac.kr.
Bong-Hwa
BH
Kim
Pyong-Gon
PG
Moon
Jeong-Eun
JE
Lee
Soyoung
S
Lee
Sook-Kyung
SK
Kim
Jong Kwon
JK
Lee
Sang-Hyun
SH
Kim
Moon-Chang
MC
Baek
D000818:Animals; D015415:Biomarkers / Q000097:blood; D004785:Environmental Pollutants / Q000633:toxicity*; D006023:Glycoproteins / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017669:Mercury Compounds / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D040901:Proteomics
D015415:Biomarkers; D004785:Environmental Pollutants; D006023:Glycoproteins; D017669:Mercury Compounds; D008767:Methylmercury Compounds; C034211:cinnabar
biomarkers; glycoprotein; label-free quantification; mercury; serum protein