Potential role of pyrroline 5-carboxylate in regulation of collagen biosynthesis in cultured human skin fibroblasts

• Published in: Comparative biochemistry and physiology. Part A, Molecular & integrative physiology Molecular & integrative physiology, 2000-02, Vol.125 (2), p.265-271
• Main Authors: Miltyk, W, Pałka, J.A
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Collagen; Collagen - biosynthesis; Collagen synthesis; Culture Media, Serum-Free; DNA synthesis; Fasting; fibroblast; Fibroblasts - drug effects; Fibroblasts - metabolism; Humans; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Insulin-like growth factor-I; Male; Pyrroles - metabolism; Pyrroles - pharmacology; Pyrroline 5-carboxylate; Rat serum; Rats; Rats, Wistar; Skin - cytology
• ISSN: 1095-6433; 1531-4332
• DOI: 10.1016/S1095-6433(99)00181-6

Although insulin-like growth factor-I (IGF-I) is known as an important stimulator of collagen biosynthesis in collagen-producing cells, the mechanism and endpoints by which it regulate the process remain largely unknown. Serum of acutely fasted rats contained reduced amount of IGF-I (72±16 ng/ml) and showed about 75% reduced ability to stimulate collagen and DNA synthesis in confluent human skin fibroblasts in comparison to the effect of control rat serum (IGF-I, 168±19 ng/ml). An addition of IGF-I (at least 40 ng/ml) to fasted rat serum restored its mitogenic activity but could not restore its ability to stimulate collagen biosynthesis to control values during 24 h of incubation. However, when the cells were incubated in fasted rat serum supplemented with 40 ng/ml of IGF-I for 48 h, collagen biosynthesis was restored to control values. It suggests that the stimulatory role of IGF-I in collagen biosynthesis undergo indirectly. We considered pyrroline-5-carboxylate (P5C) as a candidate to play a direct role in this process. Since IGF-I and P5C are known to be decreased in serum of fasted rats it seems that the action of IGF-I on collagen biosynthesis may involve participation of P5C. We have found that serum of fasted rats (showing low level of P5C) supplemented with 1 mmol/l P5C induced collagen biosynthesis in confluent human skin fibroblasts during 24 h to control values. Supporting evidence comes from the experiment showing stimulatory action of P5C on collagen biosynthesis in fibroblasts cultured in serum-free medium. Our results postulate potential role of P5C in regulation of collagen biosynthesis and indicate participation of this molecule in the pathway of IGF-I action in this process.