Circulating Insulin-Like Growth Factor Binding Proteins (IGFBPs) 1 and 2 Induced in Vitamin C-Deficient or Fasted Guinea Pigs Inhibit IGF-I Action in Cultured Cells

Abstract

Collagen gene expression and proteoglycan synthesis are decreased in vitamin C-deficient guinea pigs losing weight and in fasted guinea pigs receiving ascorbate. Sera from such guinea pigs contain an insulin-like growth factor (IGF)-I-reversible inhibitor of collagen, proteoglycan and DNA synthesis and elevated levels of 29 and 35-kDa IGF binding proteins (IGFBPs). We now have identified the induced proteins as IGFBPs 1 and 2 and investigated their role as inhibitors. Guinea pig sera were treated with antibodies to IGFBPs 1 and 2 and antibody-IGFBP complexes were removed by passage through a Protein A-Sepharose column. Inhibitor content of fasted and scorbutic sera, and Protein A pass-through fractions derived from them, was assessed by their level of stimulation of DNA and collagen synthesis in 3T3 cells, compared to analogously treated normal guinea pig serum. Removal of IGFBP-1 from scorbutic serum reversed inhibition of collagen and DNA synthesis by more than half but removal of IGFBP-2 was less effective. Removal of both IGFBPs reversed inhibition almost completely. Similar results were obtained with fasted guinea pig serum. Conversely, purified rat IGFBPs 1 and 2 inhibited DNA and collagen synthesis in cells cultured in normal guinea pig serum or IGF-I-stimulated DNA synthesis, with IGFBP-1 being more potent. Thus, IGFBP-1 and, to a lesser extent IGFBP-2, cause inhibition of IGF-I action by sera from fasted and scorbutic guinea pigs and may inhibit collagen gene expression in vivo.

Favorable effect of dietary vitamin C on bone mineral density in postmenopausal women (KNHANES IV, 2009): discrepancies regarding skeletal sites, age, and vitamin D status

“…Some studies of humans also showed that high plasma levels or dietary intake of antioxidants is associated with increased bone mineral density [13][14][15]. In addition, vitamin C is a cofactor in collagen formation and hydroxylation of lysine and proline [16], which are important for bone maintenance [17]. This nutrient also stimulates in vitro osteoblast differentiation and alkaline phosphatase activity, thereby contributing to bone formation [18,19].…”

Preincubation with sodium ascorbate potentiates insulin-dependent PKB/Akt and c-Jun phosphorylation in L6 rat myoblasts challenged with reactive oxygen/nitrogen species

“…Peterkofsky et al (1991) reported elevated levels of the insulin like growth factor (IGF)-binding proteins (IGFBPs) in vitamin C deficient guinea pigs (this species, similarly to humans is unable to form endogenous AA). Moreover, when these IGFBPs were added to the cultured cells, they inhibited IGF-1-mediated growth (Peterkofsky et al, 1994). Notably, IGF-1 is a well known and potent mitogen for the undifferentiated muscle cells (Engert et al, 1996).…”

Subcellular distribution of the insulin‐like growth factor (IGF) binding proteins (IGFBPs) 2 and 3 in articular chondrocytes

“…IGFBP-2 was found in the cytoplasmic fraction by Western immunoblot 31 in three separate subfractionations from the same cell preparation (these were denominated I to III: for sets I and II the cells were taken from spinner culture on day 2 and for set III they were removed on day 5, as described above and in the Fig. 3 legend).…”