Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
Gene/Protein
Disease
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Query: EC:3.1.27.1 (
RNase
)
16,360
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Lactase-phlorizin hydrolase
(
LPH
) and sucrase-isomaltase (SI) are intestine-specific microvillus membrane hydrolases whose specific activities demonstrate reciprocal regulation during development but whose mechanisms of regulation have not been fully defined. To investigate transcriptional control of these two proteins, the rat
LPH
and SI genes were cloned, and antisense probes for preprocessed mRNAs (pre-mRNAs) were developed from intron sequence.
LPH
mRNA, as measured by quantitative
ribonuclease
(
RNase
) protection assays, was abundant before weaning and decreased two- to fourfold during weaning, whereas SI mRNA was first detected 14 days after birth and increased rapidly to abundant levels by age 28 days.
LPH
and SI pre-mRNA levels paralleled those of their respective mRNAs.
LPH
transcriptional rate declined during weaning, whereas that of SI increased during this time as determined by
RNase
protection assays of pre-mRNAs and nuclear run-on assays. In the adult rat,
LPH
mRNA was restricted to the jejunum and proximal ileum, whereas SI mRNA was detected throughout the small intestine, a pattern regulated by transcriptional rate as confirmed by nuclear run-on assays. Lactase and sucrase specific activities correlated well with their respective protein and mRNA concentrations in all experiments. We conclude that gene transcription plays a major role in the developmental and horizontal regulation of
LPH
and SI biosynthesis and that these two genes are regulated differently in rat small intestine.
...
PMID:Transcriptional regulation of intestinal hydrolase biosynthesis during postnatal development in rats. 794 23
We have previously shown that fetal exposure to ethanol in rats produces both structural and biochemical abnormalities in absorptive enterocytes. Among the indicators of injury are derangements in the expression of
lactase-phlorizin hydrolase
(
LPH
), which is an essential enzyme for the assimilation of milk. In an animal model of fetal alcohol syndrome, unsuckled newborn rats prenatally exposed to maternal ethanol revealed a 10- to 15-fold increase in the number of
LPH
mRNA molecules per absorptive enterocyte, compared with controls (Estrada et al., Alcohol. Clin. Exp. Res. 20:1662-1668, 1996). However, lactase activity per cell was similar in both groups. The aim of this study was to characterize the effect of prenatal exposure to ethanol on the processing of
LPH
mRNA and protein.
RNase
protection assays using 3'- and 5'-directed antisense RNA probes revealed that the
LPH
mRNA from ethanol-exposed pups is full length. However, metabolic labeling, followed by immunoprecipitation using an anti-
LPH
monoclonal antibody, demonstrated a significant alteration in
LPH
protein processing. Intestinal explants from 21-day ethanol-exposed fetuses that were chased 30 min after a [35S]methionine pulse showed greater amounts of newly synthesized
LPH
precursors (205 and 220 kDa) and low molecular weight degradation products than controls. However, despite the increases in
LPH
precursor, the amount of 130 kDa mature
LPH
was similar in ethanol-exposed and control explants. These data suggest an increase in intracellular degradation of
LPH
precursor in rats prenatally exposed to ethanol, which occurs before its insertion into the microvillus membrane. Biosynthesis of
LPH
appears to be upregulated at the transcriptional level, which overcomes the degradation of
LPH
precursor during processing.
...
PMID:Defective intracellular processing of lactase-phlorizin hydrolase protein in rats prenatally exposed to ethanol. 972 93
Numerous genes expressed by intestinal epithelial cells are developmentally regulated, and the influence that adaptive (AI) and passive (PI) immunity have in controlling their expression has not been evaluated. In this study, we tested the hypothesis that both PI and AI influenced enterocyte gene expression by developing a breeding scheme that used T and B cell-deficient recombination-activating gene (RAG) mice. RNA was isolated from the liver and proximal/distal small intestine at various ages, and the steady-state levels of six different transcripts were evaluated by
RNase
protection assay. In wild-type (WT) pups, all transcripts [Fc receptor of the neonate (FcRn), polymeric IgA receptor (pIgR), GLUT5,
lactase-phlorizin hydrolase
(
lactase
), apical sodium-dependent bile acid transporter (ASBT), and Na+/glucose cotransporter (SGLT1)] studied were developmentally regulated at the time of weaning, and all transcripts except ASBT had the highest levels of expression in the proximal small intestine. In WT suckling pups reared in the absence of PI, pIgR mRNA levels were increased 100% during the early phase of development. In mice lacking AI, the expression of pIgR and
lactase
were significantly attenuated, whereas FcRn and GLUT5 levels were higher compared with WT mice. Finally, in the absence of both passive and active immunity, expression levels of pIgR and
lactase
were significantly lower than similarly aged WT mice. In summary, we report that the adaptive and passive immune status of mice influences steady-state mRNA levels of several important, developmentally regulated enterocyte genes during the suckling and weaning periods of life.
...
PMID:Role of passive and adaptive immunity in influencing enterocyte-specific gene expression. 1296 28