Guinea pigs that are either vitamin C deficient or fasted (vitamin C supplemented), are equivalent with respect to the mechanisms responsible for decreased collagen and proteoglycan synthesis. Circulating insulin- like growth factor binding proteins (IGFBPs) induced during scurvy and fasting inhibit these functions because they interfere with IGF-I action. It was reported that one of these proteins, IGFBP-1, is phosphorylated in human tissues, and that phosphorylation influences its ability to act as an inhibitor of DNA synthesis. We examined the phosphorylation of rat IGFBP-1, which we previously found to be inhibitory, and found that rat IGFBP-1 is phosphorylated at two sites, but the presence or absence of phosphate groups did not affect its ability to bind IGF-1 or to inhibit DNA and collagen synthesis in cell culture. We also have investigated the basis for hemorrhaging of blood vessels in scorbutic guinea pigs by examining the expression of components of the basement membrane such as type IV collagen and laminin, and components of the intimal layer such as type I collagen and elastin. The expression of laminin was unaffected, but expression of the other three genes was decreased once guinea pigs began to lose weight and IGFBPs were induced. These results suggest that loss of these blood vessel components may be the cause of hemorrhaging.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC000945-26
Application #
6289060
Study Section
Special Emphasis Panel (LB)
Project Start
Project End
Budget Start
Budget End
Support Year
26
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code