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Phosphatidylinositol-Specific Phospholipase C in Fetal Membranes and Uterine Decidua

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Phosphatidylinositol-Specific Phospholipase C in Fetal Membranes and Uterine Decidua Phosphatidylinositol-specific Phospholipase C in Fetal Membranes and Uterine Decidua Gian Carlo Di Renzo, … , Paul C. MacDonald, John E. Bleasdale J Clin Invest. 1981;67(3):847-856. https://doi.org/10.1172/JCI110102. Research Article An assay procedure was developed in which phosphatidyl[2-3H]inositol was employed as substrate for the measurement of phosphatidylinositol-specific phospholipase C activity. Employing this assay, phosphatidylinositol-specific phospholipase C activity in human fetal membranes and uterine decidua was identified and characterized. The specific activity of this enzyme in amnion (4.4 μmol × mg−1 protein × h−1) was three times that in uterine decidua and more than five times that in chorion laeve. No difference was found between the specific activity of phosphatidylinositol-specific phospholipase C in placental amnion and that in reflected amnion. The products of phosphatidylinositol hydrolysis in short-term incubations were stoichiometric amounts of diacylglycerol and inositol-1,2-cyclic-phosphate plus inositol-1- phosphate. After longer periods of incubation, monoacylglycerol also was detected. Diacylglycerol lipase activity also was demonstrated in these tissues. More than 90% of phosphatidylinositol-specific phospholipase C activity of amnion tissue was recovered in the 105,000-g supernatant fraction, and optimal enzymatic activity in vitro was observed at pH 6.5-7.5 in the presence of Ca2+ (8 mM) and mercaptoethanol (4 mM). Phosphatidylinositol-specific phospholipase C activity was stimulated by fatty acids in low concentrations, but was inhibited by lysophosphatidylcholine and a variety of detergents. No effect of labor on the specific activity of phosphatidylinositol-specific phospholipase C in either fetal membranes or uterine decidua could be detected. The finding of an active phosphatidylinositol-specific phospholipase C activity in human fetal […] Find the latest version: https://jci.me/110102/pdf Phosphatidylinositol-specific Phospholipase C in Fetal Membranes and Uterine Decidua GIAN CARLo Di RENZO, JOHN M. JOHNSTON, TAKESHI OKAZAKI, JANICE R. OKITA, PAUL C. MACDONALD, and JOHN E. BLEASDALE, Cecil H. and Ida Green Center for Reproductive Biology Sciences, and the Departments of Biochemistry and Obstetrics-Gynecology, The University of Texas Southwestern Medical School, Dallas, Texas 75235 A B S T R A C T An assay procedure was developed in specific phospholipase C in either fetal membranes or which phosphatidyl[2-3H]inositol was employed as uterine decidua could be detected. The finding of substrate for the measurement of phosphatidylinositol- an active phosphatidylinositol-specific phospholipase specific phospholipase C activity. Employing this C activity in human fetal membranes and uterine assay, phosphatidylinositol-specific phospholipase C decidua is complementary to our previous finding of a activity in human fetal membranes and uterine decidua selective loss of arachidonic acid from phosphati- was identified and characterized. The specific activity dylinositol of human fetal membranes during labor. of this enzyme in amnion (4.4 umol x mg-' protein The action of phosphatidylinositol-specific phospho- x h-1) was three times that in uterine decidua and lipase C, coupled to diacylglycerol lipase action, could more than five times that in chorion laeve. No dif- provide a mechanism for the release of arachidonic ference was found between the specific activity of acid for prostaglandin biosynthesis during parturition. phosphatidylinositol-specific phospholipase C in placental amnion and that in reflected amnion. The INTRODUCTION products of phosphatidylinositol hydrolysis in short- term incubations were stoichiometric amounts of Prostaglandins or prostaglandin-related compounds diacylglycerol and inositol-1,2-cyclic-phosphate plus appear to play an important role in the initiation of inositol-l-phosphate. After longer periods of incuba- human parturition (1, 2). The obligate precursor of tion, monoacylglycerol also was detected. Diacyl- prostaglandins of the 2-series is free arachidonic acid glycerol lipase activity also was demonstrated in these (3). However, in mammalian tissues arachidonic acid is tissues. More than 90% of phosphatidylinositol-specific present predominantly in an esterified form; thus, the phospholipase C activity of amnion tissue was re- enzymatic release of free arachidonic acid is of signal covered in the 105,000-g supernatant fraction, and importance in the regulation of prostaglandin bio- optimal enzymatic activity in vitro was observed at pH synthesis (4). Human fetal membranes and uterine 6.5-7.5 in the presence of Ca2+ (8 mM) and mercapto- decidua contain an unusually high content of esterified ethanol (4 mM). Phosphatidylinositol-specific phos- arachidonic acid (5, 6); and -66% of the arachidonic pholipase C activity was stimulated by fatty acids in acid of human fetal membranes is present in the low concentrations, but was inhibited by lysophos- glycerophospholipids of these tissues (7). Greater phatidylcholine and a variety of detergents. No effect amounts of free fatty acids are found in amniotic fluid of labor on the specific activity of phosphatidylinositol- obtained during labor than in amniotic fluid obtained before labor, and the concentration of arachidonic acid in amniotic fluid during labor is disproportionately Dr. Di Renzo was a visiting fellow under the auspices of increased with the Fulbright-Hays Exchange Program. His present address is compared that of other fatty acids (6, 8). Clinica Obstetrica e Ginecologica, Policlinico Universitario, In a previous study we found that phospholipase 41100 Modena, Italy. Dr. Okita is the recipient of a predoctoral A2 of human fetal membranes exhibited substrate fellowship from the Robert A. Welch Foundation, Houston, specificity for the sn-2 arachidonoyl esters of phosphati- Tex. Address correspondence to Dr. John E. Bleasdale, dylethanolamine (9). Other evidence that phosphati- Department of Biochemistry, The Universtiy of Texas South- western Medical School, Dallas, Tex. 75235. dylethanolamine may be a storage form of arachidonic Received for publication 25 July 1980 and in revised form acid for prostaglandin biosynthesis was the finding 31 October 1980. that, during labor, there is a marked reduction in the J. Clin. Invest. X The American Society for Clinical Investigation, Inc. * 0021-9738/81/03/0847/10 $1.00 847 Volume 67 March 1981 847-856 arachidonic acid content of phosphatidylethanol- at the time of spontaneous vaginal delivery or at the time of amine in amnion the arachidonic acid elective cesarean section performed before the onset of labor. (10). However, The membranes were washed several times with ice-cold content of phosphatidylinositol in amnion also de- NaCl (0.15 M). The amnion tissue was peeled away from creases during labor (10). The possibility that phos- chorion laeve, and for some experiments the amnion was phatidylinositol also may supply arachidonic acid for divided into placental and reflected parts. The uterine prostaglandin biosynthesis during labor is attractive decidua vera was removed from the chorion laeve by sharp dissection. Employing this technique, it was found by histo- since, in many tissues, I-stearoyl-2-arachidonoyl- logic examination that the chorion laeve after dissection glycerophosphoinositol is the predominant molecular was not contaminated by decidual tissue. The separated species of this phospholipid (11). However, a phos- fetal membranes and the uterine decidua were washed with phatidylinositol-specific phospholipase A2 has not been ice-cold sucrose solution (0.32 M), blotted, and weighed. A described. it was that portion (2 g) of each tissue was cut into small pieces, placed Recently, shown when platelets in 5 ml of ice-cold sucrose (0.32 M), and homogenized for were stimulated with thrombin, phosphatidylinositol 30 s, employing a Polytron homogenizer (Brinkmann Instru- was hydrolyzed rapidly to diacylglycerol (12-15), ments, Inc., Westbury, N. Y.) with the small blade and a dial which in turn was hydrolyzed by a diacylglycerol setting of 6. The whole homogenate was centrifuged at 750 g lipase to produce free arachidonic acid (13, 16). The for 10-min (Sorvall-Superspeed RC2B centrifuge, type SS-34 rotor; DuPont Instruments-Sorvall Biomedical Div., New- hydrolysis of phosphatidylinositol is catalyzed by a town, Conn.), and the resulting supernatant fluid was re- specific phospholipase C (phosphatidylinositol phos- moved and passed through four layers of cheesecloth. In phodiesterase, EC 3.1.4.10) in a reaction leading to some experiments, an aliquot of this extract ("homogenate") the formation of diacylglycerol, myo-inositol- 1- was employed as the enzyme source. The homogenate was and centrifuged at 10,000 g for 10 min. The 10,000-g pellet phosphate myo-inositol-1,2-cyclic phosphate. (mitochondria-enriched fraction) was resuspended in sucrose Phosphatidylinositol-specific phospholipase C activity (0.32 M) and the 10,000-g supematant fraction was centri- has been demonstrated in several tissues (17-26). fuged at 105,000 g for 60 min (Beckman L2-65 centrifuge, The purpose ofthe present investigation was to identify type TiSO rotor; Beckman Instruments, Inc., Spinco Div., and to characterize, if present, phosphatidylinositol- Palo Alto, Calif.). The 105,000-g pellet (microsome-enriched fraction) was resuspended in sucrose (0.32 M) and centri- specific phospholipase C activity in human fetal fuged at 105,000 g for 60 min. The resulting pellet was resus- membranes
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