Ma X, Svegliati-Baroni G, Poniachik J, Baraona E, Lieber C S
Alcohol Research and Treatment Center, Bronx Veteran Affairs Medical Center, NY 10468, USA.
Alcohol Clin Exp Res. 1997 Oct;21(7):1204-11.
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 CNBH3 or with 170 microM 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 microM 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.
乙醛可刺激星状细胞中的胶原蛋白合成，并在酗酒者的肝脏中与前胶原形成加合物。为了评估乙醛对羧基末端前肽的修饰是否会影响其从原胶原裂解后对胶原蛋白合成发挥反馈抑制的能力，通过凝胶过滤新生大鼠10⁹颅骨成纤维细胞来源的I型原胶原的细菌胶原酶消化产物来制备前肽，并使其与250 mM乙醛和100 mM硼氢化钠或与不含还原剂的170 μM乙醛反应，以模拟体内条件。未修饰的前肽对 Ito 细胞的胶原蛋白合成产生浓度依赖性抑制。相比之下，乙醛修饰的前肽对细胞中原胶原合成的抑制作用较小，同时培养基中胶原蛋白的积累更多。与170 μM乙醛孵育，以及在较小程度上与50 mM乙醇孵育，会在星状细胞中产生可被胶原酶消化的加合物。因此，乙醛与原胶原羧基末端前肽形成加合物可能至少部分解释了乙醛对星状细胞胶原蛋白合成的刺激作用，并可能通过降低前肽对胶原蛋白合成的正常反馈调节而导致胶原蛋白积累。
