Glycosylation of P-glycoprotein in a multidrug-resistant KB cell line, and in the human tissues

Misako Ichikawa, Akihiko Yoshimura, Tatsuhiko Furukawa, Tomoyuki Sumizawa, Yukio Nakazima, Shin ichi Akiyama

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Abstract

P-glycoprotein (P-gp) is thought to transport anti-cancer drugs and to be responsible for the multidrug-resistant (MDR) phenotype. Immunohistochemistry reveals that P-gp is also expressed in normal human tissues, such as the adrenal gland, kidney, liver, and the capillary endothelium of the brain and testis. However, little is known about the structural and functional variations of P-gp in these tissues. With immunoblotting and photoaffinity labeling, we found that the molecular mass of P-gp in these tissues varied between 130-140 kDa. To clarify the post-translational modification of P-gp, we studied the biosynthesis of P-gp in a human multidrug-resistant cell line (KB-C2). We found that P-gp was produced in KB-C2 cells as a 125 kDa precursor and was slowly processed (t 1 2=45-60 min) to the mature form of 140 kDa. In the presence of tunicamycin, a 120 kDa form of P-gp was synthesized and this form was no longer processed. Treating the 125 kDa precursor form with endo-β-N-acetylglucosaminidase H (Endo H) and the 140 kDa mature form with N-glycanase diminished the molecular size of P-gp to that of the tunicamycin-treated form. N-Glycanase almost completely removed [3H]glycosamine labeling from P-gp. These data indicate that the major modification of P-gp is N-linked glycosylation. P-gps from KB-C2 cells, kidney and adrenal gland had a different lectin-binding capacity. There seems to be a variety of N-linked glycosylations in tissue and tumor P-gps.

Original languageEnglish
Pages (from-to)309-315
Number of pages7
JournalBBA - General Subjects
Volume1073
Issue number2
DOIs
Publication statusPublished - 1991 Mar 4
Externally publishedYes

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Keywords

  • (Human tissue)
  • (KB cell)
  • Glycosylation
  • Multidrug resistance
  • P-glycoprotein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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