STIMULATION OF CELL-PROLIFERATION AND INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION BY LINOLEIC-ACID

The effect of linoleic acid (LA) on gap-junction permeability, connexi n 43 mRNA level, protein level, and phosphorylation, and the numbers o f gap-junctional membrane plaques were studied in the rat liver epithe lial cell line WB-F344 to determine whether changes in these parameter s correlated with the enhanced cell growth and the inhibition of gap-j unction function. When cultured in a medium with low serum (1%), these cells exhibited a slower growth rate than in the high serum medium (7 %). Addition of linoleic acid (0.01-3 mg/ml) to the low serum medium i ncreased the growth rate and inhibited gap junctional intercellular co mmunication (GJIC) in a dose-dependent manner. In a comparison of shor t-term and long-term treatments with LA, GJIC in short-term treated (1 h) WE cells was inhibited at 3 mg/ml LA but readily recovered by wash ing and removing LA from cells, whereas GJIC in long-term treated (6 d ays) WE cells did not recover by washing and removing LA from WE cells , Western blot analysis of connexin 43 showed that a short-term incuba tion with linoleic acid increased the relative amount of unphosphoryla ted connexin 43 protein, but a long-term incubation with linoleic acid decreased the amount of unphosphorylated connexin 43 protein and incr eased the relative;amount of hyperphosphorylated connexin 43 protein. Connexin 43 and p53 mRNA levels decreased in a time- and dose-dependen t manner in linoleic acid-treated cells. These results suggest that gr owth stimulation and gap junctional intercellular communication inhibi tion of rat liver epithelial cells by linoleic acid may be mediated in part through modulation of p53 expression and function. (C) 1997 Else vier Science Ireland Ltd.