Palmitoyl ascorbate: Selective augmentation of procollagen mRNA expressioncompared with L-ascorbate in human intestinal smooth muscle cells

The effect of 6-O-palmitoyl ascorbate on procollagen mRNA levels, collagen synthesis, and collagen secretion was investigated and compared with the ef fect of L-ascorbate in human intestinal smooth muscle (HISM) cells in vitro . Collagen synthesis, determined by the incorporation of H-3-proline into p epsin-resistant, salt-precipitated collagen, increased in a concentration-d ependent manner in response to palmitoyl ascorbate. There was a twofold inc rease in collagen synthesis at 2.5 and 5 mu M. By contrast, L-ascorbate was required at 4-5 times the concentration for the same response. However, at 20 mu M, both palmitoyl and L-ascorbate induced similar 2.7-fold increases in collagen synthesis. Palmitoyl ascorbate induced a 1.6- and 3.5-fold inc rease in steady-state levels of procollagen I and III mRNA levels respectiv ely whereas L-ascorbate had no effect. Palmitoyl ascorbate and L-ascorbate induced similar increases in the amounts of newly synthesized procollagen s ecreted into the medium and in the amounts of collagen types I, III and V a ccumulating in the cell layer. There was no Effect of either palmitoyl asco rbate or L-ascorbate on the activity of a procollagen alpha(2) (I) promoter construct transiently transfected into HISM cells. Palmitoyl ascorbate aug ments HISM cell procollagen synthesis and mRNA levels more efficiently than L-ascorbate. This property may be due to the greater resistance of the asc orbate ester to oxidation and suggests that palmitoyl ascorbate could be an important agent for studies of collagen synthesis in vitro. J. Cell. Bioch em. 73:312-320, 1999. (C) 1999 Wiley-Liss, Inc.