Changes in Argininosuccinate Lyase Gene Expression in the Rat Liver during Development

Abstract

Expression of the hepatic enzyme argininosuccinate lyase (ASL), one of the urea cycle enzymes, was analyzed during the perinatal period in the rat. To this end, ASL was purified, an ELISA assay was established to quantify the enzyme protein and a cDNA clone was used to measure the amount of specific mRNA in the liver in various stages of development. During the last few days of fetal life, both enzyme and hybridizable RNA were present at levels far below those measured in the fully differentiated adult liver. Just after birth, they increased rapidly and the mRNA accumulation, particularly, could result from an enhanced rate of transcription as suggested by the experiment with actinomycin D. This postnatal shift in ASL expression was also linked to adrenal activation at birth, as shown by adrenalectomy. However, the extent to which the ASL protein accumulated after birth appeared to be limited when compared to mRNA accumulation, suggesting control mechanisms at the translational level. Thus, during the perinatal period of the rat, both transcriptional and translational control might be implicated in the expression of the ASL gene.

Expression of the Genes of Arginine-Synthesizing Enzymes in the Rat Kidney during Development

“…0.05). Cortisol administration (20 Ìg/g) to adrenalectomized newborns restored the hepatic mRNA levels, as previously described [6], but was without any effect on the kidney mRNA levels (not shown). These results suggest that adrenals were not involved in the developmental expression of both genes in the kidney at birth.…”

“…Previous works from our laboratory have been directed toward determining the expression of the ASS and ASL genes and identifying the regulatory signals involved in their response in the fetal liver [5][6][7]. This work first presents evidence that the genes coding for ASS and ASL are also transcribed in various extra hepatic tissues during the fetal period.…”

“…Previous studies have focused on the expression of both genes in the developing liver where the corresponding enzyme activities and mRNAs appeared in the late fetal period [3][4][5]. Hormones such as glucocorticoids, glucagon and insulin [5][6][7] were shown to play an essential role in the developmental expression of hepatic ASS and ASL genes. Particularly, glucocorticoids suppression at birth could inhibit the development of the ASL protein and mRNA levels in the newborn liver [6].…”

“…Hormones such as glucocorticoids, glucagon and insulin [5][6][7] were shown to play an essential role in the developmental expression of hepatic ASS and ASL genes. Particularly, glucocorticoids suppression at birth could inhibit the development of the ASL protein and mRNA levels in the newborn liver [6]. Little is known about what happens in other tissues during development.…”

Developmental Control of Argininosuccinate Lyase Gene by Methylation

“…This enzyme activity appears in hepatocytes during the late fetal period, as do other ureogenic enzymes, in order to prepare the organism for independent life. A previous study showed that ASL activity and amount, as well as specific mRNA could be detected at a low level in the rat fetus liver as early as day 17.5 of gestation [1]. ASL activities and the corresponding mRNA levels measured in 18.5-and 20.5-day-old fetuses represented, respectively, about 15 and 35% of the adult levels.…”