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RETINOIC ACID-INDUCED STRESS PROTEIN SYNTHESIS IN THE MOUSE

机译:维甲酸诱导小鼠体内应力蛋白的合成

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We have previously demonstrated that stress proteins (SPs) are synthesized in tissues in which malformations are later observed following treatment with the developmental toxicant, retinoic acid (RA), on day 11 of gestation (GD 11). These proteins were not synthesized in tissues which did not present with malformations near partuition. The purpose of the present investigation was to determine if this correlation between early SP synthesis and later malformation was present at other times during gestation. CD-1 strain mice were dosed orally with corn oil or 100 mg/kg body weight RA on GD 10 or 13. Some of the mice in each group were given an intraperitoneal injection of H-3-leucine to label embryonic protein synthesis one hour after dosing with RA. These animals were sacrificed 1.5 hour later, and embryonic protein synthesis was determined by two-dimensional gel electrophoresis followed by autoradiography. Other animals in each group were sacrificed on day 17 of gestation, and fetuses were examined for the presence of malformations. Following treatment with RA on day 10 of gestation, malformations were observed in the forelimbs, the hindlimbs and the tail; heart defects were not observed. SPs of 20-25,000 and 90,000 relative molecular mass (Mr) were synthesized in the forelimb bud and tail; in addition, a second low molecular weight (20-25,000) and a 84,000 Mr SPs were synthesized in forelimb buds. No SPs were synthesized in the hindlimb bud or the heart. Following RA treatment on GD 13, cleft palate was observed in 58% of fetuses; no other malformations were found. Proteins of 34,000, 84,000 and 90,000 Mr were synthesized in craniofacial tissue; SPs were not observed in forelimb bud, hindlimb bud, heart or tail tissues at this time. Therefore, it appears that there may be a correlation between tissue-specific SP synthesis early in organogenesis and the presence of a malformation later in gestation. [References: 48]
机译:我们先前已经证明,应激蛋白(SPs)在妊娠第11天(GD 11)用发育性有毒物质视黄酸(RA)处理后在其中观察到畸形的组织中合成。这些蛋白质不是在分娩附近没有畸形的组织中合成的。本研究的目的是确定在妊娠期间其他时间是否存在早期SP合成与后期畸形之间的这种相关性。在GD 10或13上,给CD-1品系小鼠口服玉米油或100 mg / kg体重RA,每组中的一些小鼠腹膜内注射H-3-亮氨酸以标记胚胎蛋白合成一小时。用RA给药后。 1.5小时后处死这些动物,并通过二维凝胶电泳,然后进行放射自显影来测定胚胎蛋白的合成。在妊娠第17天处死每组中的其他动物,并检查胎儿是否存在畸形。妊娠第10天用RA治疗后,在前肢,后肢和尾巴观察到畸形。没有观察到心脏缺陷。在前肢的花蕾和尾巴中合成了20-25,000和90,000相对分子质量(Mr)的SP。此外,在前肢芽中合成了第二个低分子量(20-25,000)和84,000个Mr SPs。在后肢芽或心脏中没有合成SP。 RA对GD 13进行RA治疗后,有58%的胎儿出现pa裂;没有发现其他畸形。在颅面组织中合成了34,000、84,000和90,000 Mr的蛋白质;此时在前肢芽,后肢芽,心脏或尾巴组织中未观察到SP。因此,似乎器官发生早期的组织特异性SP合成与妊娠后期的畸形存在之间可能存在相关性。 [参考:48]

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