Effects of ethanol feeding on the interaction of rat hepatocytes with laminin peptides.
Laminin, a complex glycoprotein of the extracellular matrix, contains a number of biologically active sites. These sites are involved in cell growth, attachment, differentiation, and gene expression. Our previous studies have shown that chronic ethanol consumption by rats impairs hepatocyte attachment to various components of the extracellular matrix including laminin. In this study, three synthetic peptides (PA22-2, YIGSR, and RGD) that correspond to three distinct functional sites on the laminin molecule were used to investigate the effect of ethanol consumption on their cognate receptors. Initially, varying concentrations of each peptide were incubated with isolated hepatocytes from ethanol-fed and pair-fed control rats. These hepatocytes were then assayed for the ability to attach to laminin. The results indicated that all three peptides effectively inhibited laminin-mediated cell adhesion: the degree of inhibition appeared similar between pair-fed controls and ethanol-fed animals. Of the three peptides, PA22-2 showed the most dramatic inhibition of attachment. Therefore, we investigated the ability of hepatocytes to attach directly to PA22-2 itself. Attachment of hepatocytes from ethanol-fed animals to PA22-2 was impaired by 30% after 4 days and 90% by 14 days. Conversely, no significant difference in attachment to the entire laminin molecule was observed in ethanol-fed animals at these early time points. These results indicated that the ethanol-induced impairment of hepatocyte attachment to laminin may be caused by the decreased interaction of hepatocytes with specific functional sites on the laminin molecule and that specific receptors on the hepatocyte may be affected differently.(ABSTRACT TRUNCATED AT 250 WORDS)
Xu
D
D
Liver Study Unit, Department of Veterans Affairs Medical Center, Omaha, NE 68105.
Sorrell
M F
MF
Clemens
D L
DL
Casey
C A
CA
Tuma
D J
DJ
D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D007797:Laminin / Q000502:physiology*; D008099:Liver / Q000503:physiopathology*; D008297:Male; D010446:Peptide Fragments / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017474:Receptors, Laminin / Q000502:physiology*
D007797:Laminin; D010446:Peptide Fragments; D017474:Receptors, Laminin