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Altered levels of phosphoinositide metabolites and activation of guanine‐nucleotide dependent phospholipase C in rat hepatic tumors
Author(s) -
Lalwani Narendra D.,
Hylemon Philip B.,
Strom Stephen C.
Publication year - 1991
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041470222
Subject(s) - inositol , phosphatidylinositol , second messenger system , diacylglycerol kinase , phospholipase c , biology , phosphoinositide phospholipase c , gtp' , biochemistry , phospholipid , cytosol , nucleotide , phospholipase , endocrinology , chemistry , medicine , signal transduction , receptor , enzyme , protein kinase c , membrane , gene
The metabolism of phosphatidylinositol was studied in normal quiescent hepa‐tocytes, hepatocellular carcinomas induced by single dose of diethylnitrosamine, followed by 2‐acetylaminofluorene and partial hepatectomy (Solt‐Farber model), and in an established hepatoma cell line, JB1. The JB1 hepatoma cell line and hepatocellular carcinomas demonstrated a 4‐ to 5‐fold higher rate of turnover of [ 3 H]‐inositol and [ 3 H]‐glycerol than the control hepatocytes. Significantly, elevated levels of second messengers inositol 1,4,5‐trisphosphate and sn‐1,2‐diacylglycerol were noted in hepatic tumor cells within 4 hr of labeling with precursor molecules, whereas no detectable level of 3 H‐labelled inositol trisphos‐phate was noted in quiescent hepatocytes, even after incubation with 10 mM LiCl for 30 min. Approximately 2.5‐fold higher specific activities of a guanine nucleotide and Ca +2 dependent phosphatidylinositol 4,5‐bisphosphate specific phospholipase C were detected in the hepatocellular carcinoma cells. The cellular location of the phospholipase C activity was also different, being membrane bound in hepatocytes and equally distributed between cytosolic and membrane factions in the hepatomas. These data are consistent with the hypothesis that the enhanced production of diacylglycerol and inositol 1,4,5‐trisphosphate in hepa‐tocellular carcinomas may be due to the activation of a guanine nucleotide dependent phosphatidylinositol 4,5‐bisphosphate specific phospholipase C. These data are the first to compare phosphoinositide turnover in normal liver and hepatic tumor cells and suggest that the sustained levels of second messengers is closely associated with the transformation and enhanced growth rate in hepatic tumor cells.