Effect of heparin-derived oligosaccharide on vascular smooth muscle cell proliferation through inhibition of PKC-alpha expression.
- Author:
Li LI
1
;
Ting GAO
;
Shu-ying HE
;
Guang-lin XU
;
Li-na YANG
Author Information
1. School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Cattle;
Cell Cycle;
drug effects;
Cell Proliferation;
drug effects;
Cells, Cultured;
G1 Phase;
drug effects;
Heparin;
pharmacology;
Muscle, Smooth, Vascular;
cytology;
metabolism;
Oligosaccharides;
pharmacology;
Protein Kinase C-alpha;
genetics;
metabolism;
Proto-Oncogene Proteins c-fos;
genetics;
metabolism;
Proto-Oncogene Proteins c-jun;
genetics;
metabolism;
Proto-Oncogene Proteins c-myc;
genetics;
metabolism;
RNA, Messenger;
metabolism;
Signal Transduction
- From:
Acta Pharmaceutica Sinica
2012;47(8):993-1000
- CountryChina
- Language:English
-
Abstract:
In this study, the effect of heparin-derived oligosaccharide (HDO) on bovine vascular smooth muscle cell (VSMC) proliferation and signal transduction mechanism involved were investigated. The levels of PKC-alpha protein and mRNA were determined by cell-based ELISA, RT-PCR, Western blotting and immunocytochemical methods. Meanwhile, mRNA levels of c-jun, c-myc and c-fos were assayed by RT-PCR method. The results showed that HDO inhibited newborn calf serum (NCS)-induced expression of PKC-alpha and proto-oncogenes, which may be one of the mechanisms for the inhibition of VSMC proliferation by HDO. Flow cytometry analysis indicated that HDO blocked NCS-induced cell cycle progression by arresting cells at G0/G1 phase. The results imply that HDO inhibits VSMC proliferation by moderating the gene level of PKC-alpha, eventually inhibiting proto-oncogene mRNA expression and blocking G1/S transition.