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Down‐regulation of mannosylphospho dolichol synthase (DPMS) in tunicamycin treated capillary endothelial cells
Author(s) -
Banerjee Dipak K,
Martinez Juan A,
Banerjee Aditi,
Baksi Krishna
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.809.3
Subject(s) - tunicamycin , dolichol , angiogenesis , biology , cell cycle , cancer research , pharmacology , chemistry , microbiology and biotechnology , cell , apoptosis , medicine , biochemistry , biosynthesis , enzyme , unfolded protein response
The exact mechanism of switching to a new angiogenic phenotype during tumor growth is currently unknown. But, we have observed a direct relationship between the dolichol cycle and the cell cycle dynamics during in vitro angiogenesis. A non‐transformed capillary endothelial cell line when exposed to 2mM 8Br‐cAMP the cell proliferation enhanced ∼70% with one‐half of the cell population in the S phase. A significant increase in the lipid‐linked oligosaccharide (LLO) biosynthesis and turnover, and the expression of cell surface N‐glycans was also observed. Mannosylphospho dolichol synthase (DPMS) activity was also upregulated. The objective of the present study is to evaluate the status of the DPMS during anti‐angiogenic response of tunicamycin. To test this hypothesis we have examined the DPMS activity in tunicamycin treated cells as a function of time. The DPMS activity in cells has been depleted well before the induction of apoptosis. Examination of DPMS expression by Western blotting indicated down regulation of DPMS by 70–80% within 3 hours of tunicamycin treatment. Furthermore, there was no trace of DPMS after 12 hours of tunicamycin treatment. We, therefore, conclude that DPMS is an angiogenesis sensor. Supported by the grants NIH U54‐CA096297 and the Susan G. Komen Breast Cancer Foundation BCTR5820 (DKB), and NIH/NCRR/RCMI grant G12‐RR03035 (KB).