Plasma membrane form of phosphatidate phosphohydrolase: a possible role in signal transduction during liver fibrogenesis.

Abstract

1. Several growth factors important in liver regeneration and fibrosis stimulate phospholipase D in plasma membranes via a receptor/G-protein-coupled mechanism resulting in hydrolysis of phosphatidylcholine to phosphatidate. Phosphatidate can be further hydrolysed to diacylglycerol by phosphatidate phosphohydrolase. Phosphatidate and diacylglycerol can act as 'second-messengers' and regulation of phosphatidate phosphohydrolase activity could control the balance between them. 2. A form of phosphatidate phosphohydrolase, located in the plasma membrane and insensitive to inhibition by N-ethylmaleimide, has recently been identified that is distinct from the 'metabolic' form, which is present in the cytosol and microsomes and is sensitive to N-ethylmaleimide. 3. We have investigated the hypothesis that the balance between regeneration and fibrosis is, in part, determined by the activity of plasma membrane phosphatidate phosphohydrolase through its effect on the phosphatidate/diacylglycerol ratio. N-Ethylmaleimide-insensitive and -sensitive phosphatidate phosphohydrolase activities were measured in three hepatic conditions characterized by regeneration and/or fibrosis: alcoholic liver disease in humans (regeneration and fibrosis) and rat livers after either acute CCl-4-induced injury (regeneration) or common bile duct ligation (fibrosis). 4. In patients with alcoholic liver disease, N-ethylmaleimide-insensitive phosphatidate phosphohydrolase activity was higher in cirrhotic biopsies (5.82 +/- 0.3 nmol of Pi min-1 mg-1 of protein, n = 19) than in non-cirrhotic biopsies (2.17 +/- 0.2, n = 23) or in wedge biopsies from healthy subjects undergoing routine cholecystectomy (2.16 +/- 0.5, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: C P Day, A D Burt, A S Brown, M K Bennett, D J Farrell, O F James, S J Yeaman
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 85 Issue 3 Pg. 281-7 (Sep 1993) ISSN: 0143-5221 [Print] England
• PMID: 8403799 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbon Tetrachloride
• Phosphatidate Phosphatase

Topics

• Animals
• Carbon Tetrachloride
• Cell Membrane (enzymology)
• Disease Models, Animal
• Fatty Liver, Alcoholic (etiology)
• Fibrosis (chemically induced)
• Humans
• Liver (drug effects, pathology)
• Liver Cirrhosis, Alcoholic (enzymology, etiology)
• Liver Diseases, Alcoholic (enzymology)
• Liver Regeneration (physiology)
• Phosphatidate Phosphatase (physiology)
• Rats
• Rats, Wistar
• Signal Transduction (physiology)