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PpGalNacT2 participating in vanadium-induced HL-60 cell differentiation.
- Source :
-
Molecular biology reports [Mol Biol Rep] 2011 Mar; Vol. 38 (3), pp. 1483-9. Date of Electronic Publication: 2010 Sep 29. - Publication Year :
- 2011
-
Abstract
- The current study demonstrates vanadium plays the role of antitumor, and its antitumor effect is dosage-dependent. N-acetyl-galactosamine-transferase 2 (polypeptide: N-acetyl-α-galactosaminyl-transferases 2, ppGalNAc-T2) is a member of ppGalNAcTs (polypeptide: N-acetyl-α-galactosaminyl-transferases) family, which proves to play a vital role in the tumor emergence and development process. In this study, we focused on ppGalNAc-T2 and vanadium and aimed to determine whether ppGalNAc-T2 is correlated with vanadium's antitumor effect. We discovered that ppGalNAc-T2 changed with the variation of HL-60 cell growth induced by vanadium at mRNA level. Peanut agglutinin (PNA) is an exogenous lectin. PpGalNacT2 can be indirectly recognized by PNA. By means of flow cytometry and immunofluorescent staining, we found the deviation of PNA binding increased significantly at high concentration vanadium. Then we docked one of the possible compound substances of vanadium onto the body, VO(3) (molecular formula O(13)V(4), partial vanadate tetramer) and ppGalNAcT2, and simulated them via molecular dynamics, which showed that VO(3) may inhibit the activity of the enzyme by stemming conformational changes of a key loop of ppGalNAcT2. To sum up, our results suggested that ppGalNacT2 participated in vanadium induced HL-60 cell differentiation, which might be able to provide a new mechanism of vanadium's antitumor effect.
- Subjects :
- Cell Proliferation drug effects
Flow Cytometry
Fluorescein-5-isothiocyanate metabolism
Fluorescence
Gene Expression Regulation, Enzymologic drug effects
HL-60 Cells
Humans
Lectins metabolism
Models, Molecular
N-Acetylgalactosaminyltransferases chemistry
N-Acetylgalactosaminyltransferases genetics
Peanut Agglutinin metabolism
Pliability drug effects
Polysaccharides metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Polypeptide N-acetylgalactosaminyltransferase
Cell Differentiation drug effects
N-Acetylgalactosaminyltransferases metabolism
Vanadium pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4978
- Volume :
- 38
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular biology reports
- Publication Type :
- Academic Journal
- Accession number :
- 20878478
- Full Text :
- https://doi.org/10.1007/s11033-010-0255-3