Molecular insights into beta-galactoside alpha2,6-sialyltransferase secretion in vivo.
Beta-galactoside alpha2,6-sialyltransferase (ST6Gal I), which is highly expressed in the liver, is mainly cleaved by Alzheimer's beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and secreted into the serum. During our studies to elucidate the molecular mechanism underlying the cleavage and secretion of ST6Gal I, we hypothesized that plasma ST6Gal I may represent a sensitive biomarker for hepatopathological situations. In the present study, we used recently developed sandwich ELISA systems that specifically detect the soluble cleaved form of ST6Gal I in plasma. We found that the level of plasma ST6Gal I was increased in two different types of liver injury models. In zone 1 hepatocyte-injured rats, the level of plasma ST6Gal I was increased together with acute phase reactions. Meanwhile, in zone 3 hepatocyte-injured rats, ST6Gal I secretion was most likely triggered by oxidative stress. Taken together, we propose two possible mechanisms for the upregulation of plasma ST6Gal I in hepatopathological situations: one accompanied by acute phase reactions to increase hepatic ST6Gal I expression and the other triggered by oxidative stress in the liver. We also found that the serum level of ST6Gal I in hepatitis C patients was correlated with the activity of hepatic inflammation.
Kitazume
Shinobu
S
Glyco-chain Functions Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. shinobuk@riken.jp
Oka
Ritsuko
R
Ogawa
Kazuko
K
Futakawa
Satoshi
S
Hagiwara
Yoshiaki
Y
Takikawa
Hajime
H
Kato
Michio
M
Kasahara
Akinori
A
Miyoshi
Eiji
E
Taniguchi
Naoyuki
N
Hashimoto
Yasuhiro
Y
D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001969:Bromobenzenes / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006526:Hepatitis C / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000502:physiology*; D020005:Propanols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012799:Sialyltransferases / Q000378:metabolism / Q000502:physiology*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D001969:Bromobenzenes; D020005:Propanols; C006463:allyl alcohol; D006861:Hydrogen Peroxide; C032036:bromobenzene; D012799:Sialyltransferases; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase