COLLAGEN-SYNTHESIS BY LIVER STELLATE CELLS IS RELEASED FROM ITS NORMAL FEEDBACK-REGULATION BY ACETALDEHYDE-INDUCED MODIFICATION OF THE CARBOXYL-TERMINAL PROPEPTIDE OF PROCOLLAGEN
Xl. Ma et al., COLLAGEN-SYNTHESIS BY LIVER STELLATE CELLS IS RELEASED FROM ITS NORMAL FEEDBACK-REGULATION BY ACETALDEHYDE-INDUCED MODIFICATION OF THE CARBOXYL-TERMINAL PROPEPTIDE OF PROCOLLAGEN, Alcoholism, clinical and experimental research, 21(7), 1997, pp. 1204-1211
Acetaldehyde stimulates collagen synthesis in stellate cells and forms
adducts with procollagen in the liver of alcoholics, To assess the po
ssibility that modification of the carboxyl-terminal propeptide by ace
taldehyde affects its capacity to exert a feedback inhibition of colla
gen synthesis after splitting from procollagen, the propeptide was pre
pared by gel filtration of the bacterial collagenase digests of procol
lagen type I (obtained from 10(9) calvaria fibroblasts of newborn rats
) and reacted with either 250 mM acetaldehyde and 100 mM CNBH3 or with
170 mu M acetaldehyde without reducing agents, to mimick in vivo cond
itions, The unmodified propeptide produced a concentration-dependent i
nhibition of collagen synthesis by Ito cells, By contrast, the acetald
ehyde-modified propeptide produced a lesser inhibition of procollagen
synthesis in the cells, associated with a greater accumulation of coll
agen in the media, The incubation with 170 mu M acetaldehyde and, to a
lesser extent, 50 mM ethanol produced collagenase-digestible adducts
in stellate cells, Thus, the formation of acetaldehyde adducts with th
e carboxyl-terminal propeptide of procollagen may account, at least in
part, for the stimulatory effect of acetaldehyde on collagen synthesi
s by stellate cells and may lead to collagen accumulation through a de
crease of the normal feedback regulation of collagen synthesis by the
propeptide.