Potential role of pyrroline 5-carboxylate in regulation of collagen biosynthesis in cultured human skin fibroblasts.
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.
Miltyk
W
W
Department of Medicinal Chemistry, Medical Academy of Białystok, Kilińskiego 1, 15-230, Białystok, Poland.
Palka
J A
JA
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D016895:Culture Media, Serum-Free; D005215:Fasting; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D011758:Pyrroles / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000166:cytology
D016895:Culture Media, Serum-Free; D011758:Pyrroles; C015485:delta-1-pyrroline-5-carboxylate; D007334:Insulin-Like Growth Factor I; D003094:Collagen