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Collagen Synthesis by Liver Stellate Cells Is Released from Its Normal Feedback Regulation by Acetaldehyde‐Induced Modification of the Carboxyl‐Terminal Propeptide of Procollagen
Author(s) -
Ma Xiaoli,
SvegliatiBaroni Gianluca,
Poniachik Jaime,
Baraona Enrique,
Lieber Charles S.
Publication year - 1997
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1997.tb04439.x
Subject(s) - acetaldehyde , procollagen peptidase , collagenase , chemistry , protein precursor , hepatic stellate cell , biochemistry , type i collagen , interstitial collagenase , ethanol , endocrinology , enzyme , biology
Acetaldehyde stimulates collagen synthesis in stellate cells and forms adducts with procollagen in the liver of alcoholics. To assess the possibility that modification of the carboxyl‐terminal propeptide by acetaldehyde affects its capacity to exert a feedback inhibition of collagen synthesis after splitting from procollagen, the propeptide was prepared by gel filtration of the bacterial collagenase digests of procollagen type I (obtained from 10 9 calvaria fibroblasts of newborn rats) and reacted with either 250 mM acetaldehyde and 100 mM CNBH 3 or with 170;μM acetaldehyde without reducing agents, to mimick in vivo conditions. The unmodified propeptide produced a concentration‐dependent inhibition of collagen synthesis by Ito cells. By contrast, the acetaldehyde‐modified propeptide produced a lesser inhibition of procollagen synthesis in the cells, associated with a greater accumulation of collagen in the media. The incubation with 170 μM acetaldehyde and, to a lesser extent, 50 mM ethanol produced collagenase‐digestible adducts in stellate cells. Thus, the formation of acetaldehyde adducts with the carboxyl‐terminal propeptide of procollagen may account, at least in part, for the stimulatory effect of acetaldehyde on collagen synthesis by stellate cells and may lead to collagen accumulation through a decrease of the normal feedback regulation of collagen synthesis by the propeptide.