NDLI: Potentiation of angiogenic switch in capillary endothelial cells by cAMP: A cross-talk between up-regulated LLO biosynthesis and the HSP-70 expression

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Glycoconjugate Journal : Volume 23, Issue 1-2, February 2006

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Potentiation of angiogenic switch in capillary endothelial cells by cAMP: A cross-talk between up-regulated LLO biosynthesis and the HSP-70 expression

Content Provider	Springer Nature Link
Author	Martínez, Juan A. Tavárez, José J. Oliveira, Caroline M. Banerjee, Dipak K.
Copyright Year	2006
Abstract	During tumor growth and invasion, the endothelial cells from a relatively quiescent endothelium start proliferating. The exact mechanism of switching to a new angiogenic phenotype is currently unknown. We have examined the role of intracellular cAMP in this process. When a non-transformed capillary endothelial cell line was treated with 2 mM 8Br-cAMP, cell proliferation was enhanced by ∼70%. Cellular morphology indicated enhanced mitosis after 32–40 h with almost one-half of the cell population in the S phase. Bcl-2 expression and caspase-3, -8, and -9 activity remained unaffected. A significant increase in the Glc3Man9GlcNAc2-PP-Dol biosynthesis and turnover, Factor VIIIC N-glycosylation, and cell surface expression of N-glycans was observed in cells treated with 8Br-cAMP. Dol-P-Man synthase activity in the endoplasmic reticulum membranes also increased. A 1.4–1.6-fold increase in HSP-70 and HSP-90 expression was also observed in 8Br-cAMP treated cells. On the other hand, the expression of GRP-78/Bip was 2.3-fold higher compared to that of GRP-94 in control cells, but after 8Br-cAMP treatment for 32 h, it was reduced by 3-fold. GRP-78/Bip expression in untreated cells was 1.2–1.5-fold higher when compared with HSP-70 and HSP-90, whereas that of the GRP-94 was 1.5–1.8-fold lower. After 8Br-cAMP treatment, GRP-78/Bip expression was reduced 4.5–4.8-fold, but the GRP-94 was reduced by 1.5–1.6-fold only. Upon comparison, a 2.9-fold down-regulation of GRP-78/Bip was observed compared to GRP-94. We, therefore, conclude that a high level of Glc3Man9GlcNAc2-PP-Dol, resulting from 8Br-cAMP stimulation up-regulated HSP-70 expression and down-regulated that of the GRP-78/Bip, maintained adequate protein folding, and reduced endoplasmic reticulum stress. As a result capillary endothelial cell proliferation was induced.
Starting Page	209
Ending Page	220
Page Count	12
File Format	PDF
ISSN	02820080
Journal	Glycoconjugate Journal
Volume Number	23
Issue Number	3-4
e-ISSN	15734986
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2006-01-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Angiogenesis Lipid-linked oligosaccharide N-linked glycoprotein Mannosylphosphodolichol synthase EC 2.4.1.83 cAMP Breast cancer Pathology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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