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Liver Proteomics

Volume 909 of the series Methods in Molecular Biology pp 141-150

Date:

Glycoproteins and Glycosylation: Apolipoprotein C3 Glycoforms by Top-Down MALDI-TOF Mass Spectrometry

  • Yan ZhangAffiliated withDepartment of Biochemistry, Molecular Biology and Biophysics, University of MinnesotaDepartment of Laboratory Medicine, Harvard Medical School, Children’s Hospital Boston
  • , Alan R. SinaikoAffiliated withDepartment of Pediatrics, University of Minnesota
  • , Gary L. NelsestuenAffiliated withDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Email author 

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Abstract

Apolipoprotein C3 (ApoC3) is synthesized in liver so that levels or isoform distributions may constitute indicators of liver pathogenesis. The glycoforms of intact protein ApoC3 in serum or plasma can be readily analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry after a one-step extraction using a C4 reverse-phase ZipTip. Glycoform distributions were sensitive to severe systemic diseases such as sepsis or liver diseases such as chronic hepatitis C and alcoholic liver cirrhosis. Glycoisoform distributions were also altered in persons with elevated body mass index and were corrected to normal distribution by metformin, a common drug used for diabetes therapy. This simple method may offer an approach to analysis of health and the mechanism of drug therapies.

Key words

Glycoforms Glycosylation Apolipoprotein C3 Plasma biomarker Mass spectrometry MALDI-TOF Protein profiling Liver diseases