title: Selenium-binding protein 1: a sensitive urinary biomarker to detect heavy metal-induced nephrotoxicity.
abstract: Identifying novel biomarkers to detect nephrotoxicity is clinically important. Here, we attempted to identify new biomarkers for mercury-induced nephrotoxicity and compared their sensitivity to that of traditional biomarkers in animal models. Comparative proteomics analysis was performed in kidney tissues of Sprague-Dawley rats after oral treatment with HgCl2(0.1, 1, or 5 mg/kg/day) for 21 days. Kidney cortex tissues were analyzed by two-dimensional gel electrophoresis/matrix-assisted laser desorption/ionization, and differentially expressed proteins were identified. The corresponding spots were quantitated by RT-PCR. Selenium-binding protein 1 (SBP1) was found to be the most markedly upregulated protein in the kidney cortex of rats after HgCl2administration. However, blood urea nitrogen, serum creatinine, and glucose levels increased significantly only in the 1 or 5 mg/kg HgCl2-treated groups. A number of urinary excretion proteins, including kidney injury molecule-1, clusterin, monocyte chemoattractant protein-1, and β-microglobulin, increased dose-dependently. Histopathological examination revealed severe proximal tubular damage in high-dose (5 mg/kg) HgCl2-exposed groups. In addition, urinary excretion of SBP1 significantly increased in a dose-dependent manner. To confirm the critical role of SBP1 as a biomarker for nephrotoxicity, normal kidney proximal tubular cells were treated with HgCl2, CdCl2, or cisplatin for 24 h. SBP1 levels significantly increased in conditioned media exposed to nephrotoxicants, but decreased in cell lysates. Our investigations suggest that SBP1 may play a critical role in the pathological processes underlying chemical-induced nephrotoxicity. Thus, urinary excretion of SBP1 might be a sensitive and specific biomarker to detect early stages of kidney injury.
authors: College of Pharmacy, Pusan National University, Busan, 609-735, Republic of Korea.
authors: Eui Kyung
authors: EK
authors: Lee
authors: College of Pharmacy, Hanyang University, Ansan, 426-791, Republic of Korea.
authors: Young-Jun
authors: YJ
authors: Shin
authors: College of Pharmacy, Pusan National University, Busan, 609-735, Republic of Korea.
authors: Eun Young
authors: EY
authors: Park
authors: College of Pharmacy, Pusan National University, Busan, 609-735, Republic of Korea.
authors: Nam Deuk
authors: ND
authors: Kim
authors: College of Pharmacy, Duksung Women's University, Seoul, 132-714, Republic of Korea.
authors: Aree
authors: A
authors: Moon
authors: Department of Biochemistry and Health Science, Changwon National University, Gyeongnam, 641-773, Republic of Korea.
authors: Seung Jun
authors: SJ
authors: Kwack
authors: School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors: Ji Yeon
authors: JY
authors: Son
authors: McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, ON, Canada.
authors: Sam
authors: S
authors: Kacew
authors: School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors: Byung Mu
authors: BM
authors: Lee
authors: College of Pharmacy, Hanyang University, Ansan, 426-791, Republic of Korea. onbae@hanyang.ac.kr.
authors: Ok-Nam
authors: ON
authors: Bae
authors: School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea. hkims@skku.edu.
authors: Hyung Sik
authors: HS
authors: Kim
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001806:Blood Urea Nitrogen; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity*; D019216:Metals, Heavy / Q000008:administration & dosage / Q000633:toxicity; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D051137:Selenium-Binding Proteins / Q000378:metabolism*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D019216:Metals, Heavy; D011506:Proteins; C000622413:Selenbp1 protein, rat; D051137:Selenium-Binding Proteins; D008627:Mercuric Chloride; D003404:Creatinine; D019256:Cadmium Chloride; D002945:Cisplatin
keywords: Biomarkers; Mercury chloride; Nephrotoxicity; Selenium-binding protein 1