Pharmacokinetics and biologic activities of human native and asialointerferon-beta s.
Glycoproteins are metabolized through an asialoglycoprotein metabolic pathway in vivo. They are desialylated and taken up by the liver via an asialoglycoprotein receptor. Fibroblast-derived natural human interferon-beta is a glycoprotein having a single asparagine-linked sugar chain. Although natural human interferon-beta may also be metabolized through this pathway, there is very little information about the biologic features of human asialointerferon-beta. We evaluated the pharmacokinetics and biologic activities of human native and asialointerferon-beta s. After intravenous administration to rabbits, human asialointerferon-beta was cleared from the blood circulation faster than the human native interferon-beta. More asialoprotein was distributed to the liver than the native type, but it induced less 2'5'-oligoadenylate synthetase. The human asialointerferon-beta had less activity than the human native interferon-beta on cell growth inhibition and 2'5'-oligoadenylate synthetase induction in Hep-G2 and HuH6 human hepatoblastoma cells. Southern blotting using a hepatitis B virus-transfected HuH6 cell line, HB611, revealed that the inhibition of hepatitis B virus DNA replication by the asialoprotein was weaker than that by the native protein. The results showed that the different effects exerted by the human native and asialointerferon-beta s may be a result of recognition of the sugar chains by rabbit hepatocytes or by human hepatoblastoma cells. The results also suggested that the terminal sialic acid of the sugar chains in natural human interferon-beta significantly affects its pharmacokinetics and biologic activities.
Kasama
K
K
Basic Research Laboratories, Toray Industries, Inc., Kamakura, Japan.
Utsumi
J
J
Matsuo-Ogawa
E
E
Nagahata
T
T
Kagawa
Y
Y
Yamazaki
S
S
Satoh
Y
Y
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics; D002240:Carbohydrate Sequence; D002455:Cell Division / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006515:Hepatitis B virus / Q000187:drug effects; D018197:Hepatoblastoma; D006801:Humans; D016899:Interferon-beta / Q000493:pharmacokinetics* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000494:pharmacology; D011817:Rabbits; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D004279:DNA, Viral; D009844:Oligosaccharides; C025469:asialooligosaccharides; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase