Aldehydic products of lipid peroxidation do not directly activate rat hepatic stellate cells
Olynyk, J.K., Khan, N.A., Ramm, G.A., Brown, K.E., O'Neill, R., Britton, R.S. and Bacon, B.R. (2002) Aldehydic products of lipid peroxidation do not directly activate rat hepatic stellate cells. Journal of Gastroenterology and Hepatology, 17 (7). pp. 785-790.
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Background and Aim : Activation of hepatic stellate cells (HSC) results in the transdifferentiation of the resting (quiescent) phenotype to one characterized by loss of vitamin A droplets, increased α-smooth muscle actin (SMA) expression and increased collagen production. Aldehydic products of lipid peroxidation have been shown to increase collagen production by cultured fibroblasts and by passaged HSC, but it is unclear whether these products of lipid peroxidation can initiate the activation of HSC. In the present study the effects were examined of two aldehydic products of lipid peroxidation, malondialdehyde (MDA) and 4-hydroxynonenal (HNE), on activation of rat HSC in early culture as measured by SMA and desmin expression, and collagen production.
Methods : The HSC from normal rat liver were plated in plastic wells and exposed to either MDA (5–200 µmol/L), HNE (0.1–20 µmol/L) or vehicle for either 3 or 7 days. The cells were then harvested; SMA and desmin levels were measured by western blotting. Collagen production was measured by radiolabeled proline incorporation after 6 h of aldehyde exposure.
Results: Malondialdehyde (100 and 200 µmol/L) decreased SMA expression during the 3-day and 7-day exposures compared with controls. 4-Hydroxynonenal (20 µmol/L) decreased SMA expression significantly while no effects were observed with lower concentrations compared with controls during the 3-day exposure. Seven-day exposure to HNE (0.1–20 µmol/L) failed to alter SMA expression compared with controls. Exposure to MDA or HNE did not influence desmin expression or collagen production.
Conclusions : Aldehydic products of lipid peroxidation do not directly activate HSC in early culture and alternative pathways may be responsible for HSC activation during oxidative stress.
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|Copyright:||© 2002 Blackwell Publishing Asia Pty Ltd|
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