Structural characterization of the Mr = 55,000 antigen (ZP3) of porcine oocyte zona pellucida. Purification and characterization of alpha- and beta-glycoproteins following digestion of lactosaminoglycan with endo-beta-galactosidase

The major macromolecular component of the porcine oocyte zona pellucida is a Mr = 55,000 antigen, termed ZP3, comprised of greater than 25 charge isomers. ZP3 was purified to apparent electrophoretic homogeneity from nonreduced, sodium dodecyl sulfate-treated porcine zonae pellucidae by chromatography on Sephacryl S-400 and hydroxylapatite resins. The carbohydrate moiety of purified ZP3 was comprised of a heterogeneous population of acidic lactosaminoglycans as evidenced by the saccharide composition and size distribution of glycopeptides produced by Pronase digestion of ZP3, as well as by the sensitivity of ZP3 to digestion with Escherichia freundii endo-beta-galactosidase. Endo-beta-galactosidase-digested ZP3 was resolved by gel electrophoresis into two components, termed alpha-glycoprotein and beta-glycoprotein, with Mr values (nonreduced) of 46,000 and 42,000, respectively. Each was comprised of fewer and more neutral charge isomers than ZP3. Following purification by reverse phase high performance liquid chromatography, the alpha- and beta-glycoproteins of endo-beta-galactosidase-digested ZP3 were distinguished on the basis of amino acid and carbohydrate compositions, amino-terminal sequence analyses and peptide mapping experiments, thus suggesting differences in the primary structures of their respective polypeptide moieties. Corresponding dissimilarities in the immunoreactivities of the alpha- and beta-glycoproteins toward polyclonal antisera raised against ZP3, alpha-glycoprotein, and beta-glycoprotein were revealed by competitive binding radioimmunoassays as well as by immunoblotting experiments. Collectively, the data were interpreted to indicate that the Mr = 55,000 antigen of porcine oocyte zona pellucida is in fact comprised of overlapping families of charge isomers corresponding to two structurally and immunologically distinct lactosaminoglycan-containing glycoproteins.     

同型半胱氨酸对孕鼠糖代谢的影响与机制分析

目的:探讨同型半胱氨酸(homocysteine,HCY)摄入后对孕鼠糖代谢的影响以及生物学机制分析。方法:孕鼠妊娠10 d后,将实验动物随机分为3组,每组12只,妊娠对照组(Ctrl)腹腔注射生理盐水,同型半胱氨酸高剂量组(HCYH)和同型半胱氨酸低剂量组(HCYL)腹腔注射HCY溶液,注射浓度分别为200 mg/kg·d和100 mg/kg·d,持续20 d(即为HCY20 d)后,利用血糖含量检测试剂盒和胰岛素试剂盒分别检测孕鼠空腹血糖水平、胰岛素水平;葡萄糖检测试剂盒对孕鼠葡萄糖耐量和胰岛素抵抗进行检测;蛋白免疫印迹法检测孕鼠目的蛋白过氧化物酶体增殖物激活受体γ(PPARγ)、葡萄糖转运蛋白4(GLUT4)、蛋白激酶B(AKT)、磷酸化AKT蛋白(P-AKT)的表达。结果:与Ctrl组比较,在孕鼠注射HCY后,空腹血糖水平升高、血清中胰岛素浓度下降、HOMA-β指数下降、HOMA-IR指数升高(P<0.05);摄入葡萄糖后,孕鼠血糖随时间的变化而下降,葡萄糖曲线下面积升高(P<0.05);摄入胰岛素后,孕鼠血糖随时间的变化而升高,胰岛素曲线下面积升高(P<0.05);PPARγ、P-AKT、GLUT4蛋白表达水平下降,HCYH组降低水平更为显著(P<0.05)。结论:孕鼠HCY摄入后,生物体糖代谢紊乱,AKT磷酸化表达水平抑制,HCY可能通过降低PPARγ的表达减少AKT磷酸化,导致胰岛素受体的活化,进而激活了PI3K/AKT通路,减少了脂肪组织中的GLUT4表达,增加了对于葡萄糖的摄取能力。     

Influence of blood pressure control on delivery in pregnant rats in a warm environment

The relation between blood pressure and delivery in pregnant rats was investigated when the blood pressure of pregnant rats was controlled by a pressor or antihypertensive drug in the middle or final stage of pregnancy. All of the pregnant rats studied delivered in a 23 degrees C environment in spite of blood pressure control by a pressor or antihypertensive drug. At 33 degrees C, the pregnant rats were divided into two groups whose blood pressure was increased severely (160-175 mm Hg) or moderately (145-155 mm Hg) at 10 days of pregnancy. Those in the former group delivered, but those in the latter died in the final stage of pregnancy. When the pregnant rats in the group with high blood pressure on day 10 were treated with a antihypertensive drug in the middle stage of pregnancy or with a pressor drug in the final stage, the mortality rate was 100 per cent in both cases. The delivery rate was 57 per cent when the pregnant rats were treated with a antihypertensive drug from the middle to the final stage of pregnancy. In the group with low blood pressure on day 10, all of the pregnant rats delivered when they were treated with a pressor drug in the middle stage of pregnancy. However, the delivery rate was 89 per cent when the pregnant rats were treated with antihypertensive drug in the final stage of pregnancy.     

Large-scale chemoenzymatic synthesis of blood group and tumor-associated poly-N-acetyllactosamine antigens

Poly-N-acetyllactosamines (pLNs) are common terminal sugars of many N- and O-linked glycan structures present in glycoproteins and glycolipids. Utilizing various glycosyltransferases, we developed new and efficient chemoenzymatic methods for the synthesis of pLNs in gram-scale. Specifically, the use of sialyltransferases and fucosyltransferases enabled us to synthesize and purify 24 blood group and tumor-associated pLN derivatives with alpha-(2-->3)- and alpha-(2-->6)-linked sialic acid, as well as with alpha-(1-->2)- and alpha-(1-->3)-linked fucose. All synthesized derivatives were linked to a short 2-azidoethyl spacer for further modification.     

Straightforward isolation of phosphatidyl-ethanolamine-binding protein-1 (PEBP-1) and ubiquitin from bovine testis by hydrophobic-interaction chromatography (HIC)

Isolation of phosphatidyl-ethanolamine-binding protein-1 (PEBP-1) from bovine brain was described almost three decades ago but it required a large number of steps to reach high purity. After the fractionation of bovine testis proteins by ammonium sulfate precipitation we found that PEBP-1, detected by Western blotting, was among the very few proteins still soluble at 80% ammonium sulfate saturation (3.2M). This soluble fraction (S80) was directly loaded onto a phenyl sepharose column equilibrated at the same ammonium sulfate concentration (3.2M). A stepwise elution of the retained material at 1.0, 0.5, 0.2, 0.1M ammonium sulfate in ammonium hydrogen carbonate was performed and then with ammonium hydrogen carbonate alone and finally with 50% ethylene glycol. All fractions were analyzed by SDS-PAGE and Western blotting and the fractions containing PEBP-1 was further fractionated by size exclusion chromatography on a HR75 Superdex column permitting the isolation of ubiquitin in addition to PEBP-1 as demonstrated by Western blotting and mass spectrometry. This study shows the feasibility of hydrophobic interaction chromatography (HIC) on phenyl sepharose at a very high ammonium sulfate concentration (3.2M; 80% saturation) to efficiently purify the proteins that are still soluble in these extreme conditions.     

Unique intermolecular bactericidal epitope involving the homosialopolysaccharide capsule on the cell surface of group B Neisseria meningitidis and Escherichia coli K1

The N-propionylated group B meningococcal polysaccharide mimics a unique bactericidal epitope on the surface of group B meningococci and Escherichia coli K1. This was confirmed when both the above organisms were able to absorb the bactericidal antibodies from a mouse-anti-N-propionylated group B meningococcal polysaccharide-tetanus toxoid conjugate serum. By using affinity columns it was possible to divide the conjugate antiserum into three distinct populations of both group B polysaccharide cross-reactive and non-cross-reactive antibodies, one of which contained most of the bactericidal activity. The cross-reactive (IgG1) antibodies were absorbed by an affinity column in which the group B polysaccharide was linked to the solid support by a long spacer arm, thereby isolating a population of non-cross-reactive (IgG1) antibodies. Surprisingly the above column also retained another population of non-cross-reactive (IgG2a) and (IgG2b) antibodies which contained most of the bactericidal activity. These latter antibodies were not absorbed by a similar group B polysaccharide-affinity column in which a short spacer arm was employed. Thus the above experiments not only effected a separation of highly bactericidal antibodies but also provided evidence that the long spacer arm is functional in the binding of the bactericidal antibodies to the affinity column. This indicates that the bactericidal epitope is mimicked by the group B polysaccharide in the presence of the long spacer arm, which supports the hypothesis that the epitope is polysaccharide-associated and is probably intermolecular in nature.     

Progesterone metabolism by major salivary glands of rat--I. Submandibular and sublingual glands

The metabolism of progesterone by the submandibular and sublingual salivary glands of female (nonpregnant and pregnant) and male rats was studied. The metabolism was in both sexes significantly greater in submandibular than in sublingual glands. Sex differences were not seen in sublingual glands but less metabolism was found in homogenates and microsomal fractions of female (nonpregnant and pregnant) submandibular glands compared to that of males. The metabolism did not differ between pregnant and nonpregnant female rats. The metabolites were mainly 5 alpha-pregnane-compounds. On the basis of the metabolites identified it can be concluded that rat submandibular and sublingual glands contain at least 3 alpha-, 3 beta-, 20 alpha- and 20 beta-hydroxysteroid dehydrogenase, 5 alpha- and 5 beta-steroid hydrogenase and 17 alpha-steroid hydroxylase activity. 5 alpha-steroid hydrogenase activity was significantly higher in all preparations of male submandibular glands than in females. In sublingual glands some enzyme activities showed pregnancy-related decreased.     

Maternal-perinatal interrelationships of vitamin D metabolism in rats.

In pregnant rats it has been possible to show that the distribution of cholecalciferol metabolites in their fetuses reflects the distribution of these metabolites in the blood. In these experiments, pregnant rats were maintained on a vitamin D deficient diet but were supplemented with radiolabelled cholecalciferol. The metabolites found were 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, to a lesser extent, cholecalciferol. 1,25-Dihydroxycholecalciferol was not detected in fetal tissues, despite the ability of fetal kidney homogenates to hydroxylate 25-hydroxycholecalciferol in C-1. Kidney homogenates of newborn pups were found to possess marked activity of 25-hydroxycholecalciferol-24-hydroxylase, which was retained even in hypocalcemic pups born to pregnant rats that were fed a low-calcium diet. Injection of radiolabeled cholecalciferol to newborn pups resulted in the formation of 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol. 1,25-Dihydroxycholecalciferol was not detected. Tissues thought of as target organs for vitamin D (in pregnant rats), namely, intestine, kidney and bone, were found to contain none or very little 1,25-dihydroxycholecalciferol. Mammary glands obtained from lactating rats were found to contain mainly the unchanged vitamin.     

Purification of oligouronides by immobilized L-histidine pseudoaffinity chromatography

Selective purification of alpha-(1,4)-oligogalacturonides was investigated using several pseudobioaffinity chromatography matrix with aminoacid L-histidine as pseudobiospecific ligand: (1) sepharose 4B-bisoxyran-histidine, (2) sepharose 4B-epoxy-histidine, (3) silica-oxyran-histidine and (4) CIM-disk-EDA-histidine. These anionic oligosaccharides prepared by enzymatic and chemical cleavage of polygalacturonic acid were used as models sugar in order to optimize the adsorption and elution parameters for a selective purification of bioactive oligouronides. Monolithic CIM-disk chromatography is one of the fastest liquid chromatographic method using for separation and purification of biomolecules thanks to high mass transfer rate. In this way, this new monolithic CIM-disk system with L-histidine immobilized: immobilized histidine affinity chromatography (IHAC) constitutes a good tool allowing the fast and selective purification of bioactive oligouronides.     

Evidence for the occurrence of an alkaline proteinase in kidney cortex lysosomes

A novel alkaline endoproteinase optimally active at pH 8.5 has been detected in highly pure preparations of buffalo kidney cortex lysosomes. The enzyme has been partially purified (90-fold) by solubilization with octylglucoside, acid precipitation and chromatography over DEAE sephacel and sepharose 6B. The alkaline proteinase, resistant to known inhibitors of lysosomal cathepsins is inhibited by soyabean trypsin inhibitor and phenyl methyl sulphonyl fluoride indicating that the enzyme is a serine proteinase.     

Immunochemical characteristics of alpha 2-globulin from the rat "pregnancy zone" in ontogeny

An antigen with electrophoretic mobility of alpha 2-globulins was found in the blood serum of the pregnant rats by means of electrophoresis. It is detected not only in the blood serum and tissue extracts of the pregnant rats, but occurs in low concentrations (1 microgram/ml) in the blood serum of the normal adult animals. The concentration of this protein attains the maximal values by the end of the pregnancy period. Alpha 2-globulin appears to be a protein associated with pregnancy.     

Release of biotin from biotinylated proteins occurs enzymatically and nonenzymatically in human plasma

Studies in our laboratory and others indicate that biotin is released from biotinylated proteins in vivo and in vitro in human plasma. Using immunoglobulin G (IgG) as the model protein and four different biotinylating reagents, we investigated the mechanism of release. All of the biotin bonds shared an amide link to the carboxyl group of biotin but differed in the chemical links (amide, thioether, and hydrazone) between spacer arm and the various functional groups on IgG. Biotinylated IgG was incubated with phosphate-buffered saline, plasma, or plasma treated to either inactivate enzymes or remove all macromolecules. Released biotin was separated from bound biotin by ultrafiltration and quantitated by avidin-binding assay. As judged by high-performance liquid chromatography, greater than 95% of the released avidin-binding activity was biotin. We infer that the amide bond between the biotin and the spacer arm rather than the bond attaching the spacer to the protein was cleaved. Sodium dodecyl sulfate gel electrophoresis detected no proteolytic degradation of biotinylated IgG. Neither heat inactivation of plasma nor ultrafiltration of plasma to remove macromolecules completely eliminated biotin cleavage. We conclude that cleavage of biotin from protein occurs by both enzymatic and nonenzymatic mechanisms.     

Hydrolysis of aryl beta-maltotriosides by sweet potato beta-amylase and soybean beta-amylase.

Sweet potato beta-amylase [EC 3.2.1.2, alpha 1,4-D-glucan maltohydrolase]-catalyzed hydrolyses of aryl beta-maltotriosides with substituents, NO2-, Cl-, and Br- at the o-, m-, and p-positions in the phenyl ring were studied at pH 4.8 and 25 degrees C. The hydrolyses of a few of the maltotriosides by soybean beta-amylase [EC 3.2.1.2, alpha-1,4-D-glucan maltohydrolase] were also studied at pH 5.4 and 25 degrees C. It was found that the aryl beta-maltotriosides were preferentially hydrolyzed into maltose and aryl beta-D-glucosides by both beta-amylases. The Michaelis constant Km and the molecular activity ko were determined for the hydrolyses of these maltotriosides and compared with those of maltotriose and maltotetraose. Aryl beta-maltotriosides were more rapidly hydrolyzed than maltotriose by a factor of 30--80, and more slowly hydrolyzed than maltotetraose by a factor of 10--30, depending on the kinds of substituents. The rapid hydrolysis of aryl beta-maltotrioside as compared with maltotriose may be due to the interaction of an aryl group with the subsite of beta-amylase. This is in contrast with glucoamylase [EC 3.2.1.3, alpha-1,4-D-glucan glucohydrolase] of Rhizopus niveus-catalyzed hydrolysis of phenyl beta-maltoside, whose phenyl group does not interact so much with the subsite of the enzyme.     

阻断子宫动脉建立FGR大鼠模型的研究

目的通过暂时阻断妊娠期大鼠子宫血供的方法建立子宫缺血引起胎儿生长受限的动物模型。方法根据大鼠子宫动脉是卵巢动脉的一个分支的解剖特点,于孕鼠妊娠第15天时施行手术暂时阻断卵巢动脉并于第21天行剖宫产术,术后称量新生胎仔体重及胎盘、脑、心、肝、肺、肾等重要脏器重量,对比各组间新生胎仔的预后的不同,并对照研究阻断血供10、20、30及40 min对胎仔的不同影响。结果妊娠晚期阻断孕鼠卵巢动脉20min可成功构建胎儿生长受限模型,这种方法与阻断动脉血流30或40 min相比,手术时间短,技术要求不高,胎仔死亡率与对照组差异无显著性(P>0.05)。各实验组较对照组新生胎仔体重及胎盘、各重要脏器重量均明显降低(P<0.05)。结论通过阻断卵巢动脉从而阻断子宫动脉血流,成功建立缺血缺氧性FGR孕鼠模型。该模型重复性好,操作简便,并可成功设立同体对照,为进行FGR相关的产科理论研究提供了一个有利的技术平台。     

Maternal-perinatal interrelationships of vitamins D metabolism in rats

In pregnant rats it has been possible to show that the distribution of cholecalciferol metabolites in their fetuses reflects the distribution of these metabolites in the blood. In these experiments, pregnant rats were maintained on a vitamin D deficient diet but were supplemented with radiolabelled cholecalciferol. The metabolites found were 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, to a lesser extent, cholecalciferol. 1,25-Dihydroxycholecalciferol was not detected in fetal tissues, despite that ability of fetal kidney homogenates to hydroxylate 25-hydroxycholecalciferol in C-1.Kidney homogenates of newborn pups were found to possess marked activity of 25-hydroxycholecalciferol-24-hydroxylase, which was retained even in hypocalcemic pups born to pregnant rats that were fed a low-calcium diet.Injection of radiolabeled cholecalciferol to newborn pups resulted in the formation of 5/25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol. 1,25-Dihydroxycholecalciferol was not detected.Tissues thought of as target organs for vitamin D (in pregnant rats), namely, intestine, kidney and bone, were found to contain none or very little 1,25-dihydroxycholecalciferol.Mammary glands obtained from lactating rats were found to contain mainly the unchanged vitamin.     

Selenium–Vitamin E Combination and Melatonin Modulates Diabetes-Induced Blood Oxidative Damage and Fetal Outcomes in Pregnant Rats

Oxidative stress is considered to be the main cause of diabetic complications. In the current study, we investigated the effect of selenium–vitamin E combination and melatonin on lipid peroxidation (LPO) and scavenging enzyme activity in the blood of streptozocin (STZ)-induced diabetic pregnant rats. Forty female Wistar rats were randomly divided into five groups. The first and second groups were used as the non-pregnant control and pregnant control groups, respectively. The third group was the pregnant diabetic group. Vitamin E plus selenium and melatonin were administered to the diabetic pregnant rats consisting fourth and fifth groups, respectively. Diabetes was induced on day 0 of the study by STZ. Blood samples were taken from all animals on the 20th day of pregnancy. LPO level was higher in diabetic pregnant rats than in control, although superoxide dismutase, catalase, and glutathione peroxidase activities were lower in diabetic pregnant animals than in control. LPO levels were lower both in the two treatment groups than in the diabetic pregnant rats, whereas selenium–vitamin E combination and melatonin caused a significant increase in the activities of these antioxidant enzymes (p < 0.01). In conclusion, vitamin E plus selenium seems to be a more potent antioxidant compared to melatonin in diabetic pregnant rats. Melatonin did not significantly affect the elevated glucose concentration of diabetic pregnant treated with melatonin group. Vitamin E plus selenium may play a role in preventing diabetes-related diseases of pregnant subjects.     

羊水栓塞妊娠大鼠血清中PLA2和PAF的水平变化研究

摘要 目的：探讨羊水栓塞妊娠大鼠血清中PLA2和PAF的水平变化。方法：30只健康妊娠大鼠均分为生理盐水组（A组）、羊水组（B组）及羊水胎粪混合组（C组）。将健康妊娠大鼠麻醉,麻醉效果生成后,全部切除大鼠子宫后关腹,分离出左颈总动脉,并将二通道生理记录仪与其连接,连续监测血液动力学指标,随后将生理盐水、羊水和羊水胎粪混合液腹腔静脉注射于大鼠,1小时后取大鼠肺组织,用HE、APK染色结合CK16免疫组织化学法来检测模型是否制作成功。实验前后1小时两个取血点时,在制备好的羊水栓塞模型大鼠左颈动脉插管处各取1 mL血。采取酶联免疫检测法,测定血清、羊水及羊水胎粪混合液中 PLA2、PAF 的含量。获得的数据用SPSS 20.0软件进行处理,采用配对 t 检验、协方差分析及相关回归分析对血清PLA2、PAF 的浓度进行分析。结果：B组和C组的3个血液动力学指标（动脉收缩压、舒张压及平均动脉压）均显著低于A组（P<0.05）,而B组与C组的4个血液动力学指标均无显著性差异（P>0.05）。同时,A组、B组与C组之间在心率改变方面无显著性差异（P>0.05）。HE染色中,B组与C组大鼠的肺间质显著变宽,且有充血、水肿及炎性细胞浸润,而A组无此现象。AMP染色中,B组和C组大鼠的肺小管中可见被染成蓝色的不定形物质和桃红色的角化鳞状上皮,而A组无此现象。CK16染色中,B组和C组大鼠的肺小管中,可以看到被染成黄色的颗粒和鳞状上皮,而A组无此现象。实验1小时后所取血液中,B组和C组的PLA2与PAF的含量显著高于A组（P<0.05）,且C组中升高程度更大。妊娠大鼠羊水与羊水胎粪混合液中均检测到PLA2和PAF,且羊水胎粪混合液中二者的含量均高。实验1小时前所取的血液中,PLA2和PAF浓度无相关性（P=0.762,R=0.012）,而实验1小时后所取血液中,PLA2和PAF浓度呈正相关关系（P=0.002,R=0.437）。结论：羊水栓塞妊娠模型大鼠羊水和胎粪中均有PLA2和PAF,且实验1小时后所取血液中,PLA2和PAF含量在B组和C组中显著高于A组,说明羊水和胎粪中含有使PLA2、PAF水平增高的刺激因子。     

Protein kinase CK1 from Trypanosoma cruzi

A protein kinase activity, which uses casein as a substrate, has been purified to homogeneity from the epimastigote stage of Trypanosoma cruzi, by sequential chromatography on Q sepharose, heparin sepharose, phenyl sepharose, and alpha-casein agarose. An apparent molecular weight of 36,000 was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gel filtration chromatography and sedimentation analyses demonstrated that the purified native enzyme is a monomer with a sedimentation coefficient of 2.9 S. The hydrodynamic parameters indicated that the shape of the protein is globular with a frictional ratio f/f(o) = 1.36 and a Stokes radius of 27.7 A. When two selective peptide substrates for protein kinases CK1 and CK2 were used (RRKDLHDDEEDEAM. SITA and RRRADDSDDDDD, respectively), the purified kinase was shown to predominantly phosphorylate the CK1-specific peptide. Additionally, the enzyme was inhibited by N-(2-amino-ethyl)-5-chloroisoquinoline-8-sulfonamide, a specific inactivator of CK1s from mammals. Based on these results, we concluded that the purified kinase corresponds to a parasite CK1.     

Tyrosine aminotransferase from rat liver, a purification in three steps.

Tyrosine aminotransferase from rat liver was isolated by a three step purification method involving affinity chromatography, CM-50 chromatography and G-200 gel filtration. In order to synthesize the affinity gel, the coenzyme pyridoxamine-5′-phosphate was coupled via a spacer group to a sepharose matrix. The enzyme preparation showed a single band in SDS-acrylamide gel electrophoresis and contains three multiple enzyme forms. A molecular weight of 50,000 of the tyrosine aminotransferase subunit was estimated.     

Bestatin results in pathophysiological changes similar to preeclampsia in rats via induction of placental apoptosis.

OBJECTIVE: To establish a rat preeclampsia model with fetoplacental growth restriction caused by bestatin via induction of placental apoptosis. STUDY DESIGN: 200 mg/kg/day of bestatin or saline as a control were infused intraperitoneally into pregnant Wistar rats from 15 days' gestation. In the first experiment, maternal blood pressure and proteinuria were examined during the pre- and postpartum periods. In the second experiment, cesarean sections were performed at 20 days' gestation and the weights of pups and placentas, and levels of proteinuria and placental apoptosis were examined. RESULTS: Physiological decrease of blood pressure in late pregnancy was not detected in the bestatin group but proteinuria level at 20 days' gestation was elevated. The weights of pups and placentas in the bestatin group were significantly lower than those in the controls, bestatin strongly inducing apoptosis in the placenta. CONCLUSION: Bestatin may cause a preeclampsia-like condition through induction of placental apoptosis.