Developmental regulation of lipoprotein lipase in rats

To evaluate changes in lipoprotein lipase (LPL) expression during development, levels of LPL mRNA, protein, and enzyme activity were measured in heart, epididymal fat, kidney, and brain of rats, from late gestation through 24 mo. LPL mRNA, protein, and enzyme activity were low in fetal and neonatal hearts. LPL mRNA increased 11-fold by 60 days and remained at this level thereafter; LPL protein and enzyme activity increased 10-fold by weaning, before declining to low values by 3 mo. LPL mRNA levels, protein, and enzyme activity did not change in epididymal fat from 3 wk to 21 mo. In the kidney, LPL mRNA levels were high at the end of gestation but fluctuated during the first month. LPL protein and activity were low at day 1 and rose eightfold to peak values by day 7 before decreasing to low levels by weaning. LPL mRNA levels were relatively high in fetal brains and then fell 60% during the neonatal period. LPL protein peaked at day 7 before falling 95% by weaning. Thus LPL is under complex tissue-specific regulation involving transcriptional and posttranscriptional mechanisms.

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Tissue-specific regulation of guinea pig lipoprotein lipase; effects of nutritional state and of tumor necrosis factor on mRNA levels in adipose tissue, heart and liver

Gene ◽

10.1016/0378-1119(88)90484-2 ◽

1988 ◽

Vol 64 (1) ◽

pp. 97-106 ◽

Cited By ~ 63

Author(s):

Sven Enerbäck ◽

Henrik Semb ◽

Jan Ta vernier ◽

Gunnar Bjursell ◽

Thomas Olivecrona

Keyword(s):

Adipose Tissue ◽

Tumor Necrosis Factor ◽

Guinea Pig ◽

Lipoprotein Lipase ◽

Tumor Necrosis ◽

Nutritional State ◽

Mrna Levels ◽

Tissue Specific ◽

Specific Regulation ◽

Necrosis Factor

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Gene expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in a poorly ketogenic mammal: effect of starvation during the neonatal period of the piglet

Biochemical Journal ◽

10.1042/bj3240065 ◽

1997 ◽

Vol 324 (1) ◽

pp. 65-73 ◽

Cited By ~ 12

Author(s):

Sean H. ADAMS ◽

Clarice S. ALHO ◽

Guillermina ASINS ◽

Fausto G. HEGARDT ◽

Pedro F. MARRERO

Keyword(s):

Gene Expression ◽

Enzyme Activity ◽

Small Intestine ◽

Neonatal Period ◽

Specific Activity ◽

Mrna Levels ◽

Specific Expression ◽

Order Of Magnitude ◽

Specific Expression Pattern ◽

Low Activity

The low ketogenic capacity of pigs correlates with a low activity of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase. To identify the molecular mechanism controlling such activity, we isolated the pig cDNA encoding this enzyme and analysed changes in mRNA levels and mitochondrial specific activity induced during development and starvation. Pig mitochondrial synthase showed a tissue-specific expression pattern. As with rat and human, the gene is expressed in liver and large intestine; however, the pig differs in that mRNA was not detected in testis, kidney or small intestine. During development, pig mitochondrial HMG-CoA synthase gene expression showed interesting differences from that in the rat: (1) there was a 2–3 week lag in the postnatal induction; (2) the mRNA levels remained relatively abundant through the suckling–weaning transition and at maturity, in contrast with the fall observed in rats at similar stages of development; and (3) the gene expression was highly induced by fasting during the suckling, whereas no such change in mitochondrial HMG-CoA synthase mRNA levels has been observed in rat. The enzyme activity of mitochondrial HMG-CoA synthase increased 27-fold during starvation in piglets, but remained one order of magnitude lower than rats. These results indicate that post-transcriptional mechanism(s) and/or intrinsic differences in the encoded enzyme are responsible for the low activity of pig HMG-CoA synthase observed throughout development or after fasting.

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Alterations of lipolysis and lipoprotein lipase in chronically nicotine-treated rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.2.e215 ◽

1996 ◽

Vol 270 (2) ◽

pp. E215-E223 ◽

Cited By ~ 6

Author(s):

C. Sztalryd ◽

J. Hamilton ◽

B. A. Horwitz ◽

P. Johnson ◽

F. B. Kraemer

Keyword(s):

Adipose Tissue ◽

Lipoprotein Lipase ◽

Hormone Sensitive Lipase ◽

Mrna Levels ◽

Cellular Mechanisms ◽

Fed State ◽

Epididymal Fat ◽

Hormone Sensitive ◽

Lpl Mass ◽

Fat Pads

These studies examined the cellular mechanisms for lower adiposity seen with nicotine ingestion. Rats were infused with nicotine or saline for 1 wk and adipocytes isolated from epididymal fat pads. Nicotine-infused rats gained 37% less weight and had 21% smaller fat pads. Basal lipolysis was 78% higher, whereas the maximal lipolytic response to isoproterenol was blunted in adipocytes from nicotine-infused rats. The antilipolytic actions of adenosine and the levels of serum catecholamines were unaffected by nicotine. The nicotine-induced alteration in lipolysis was not associated with any changes in hormone-sensitive lipase. Nicotine caused a 30% decrease in lipoprotein lipase (LPL) activity, without any changes in LPL mass or mRNA levels, in epididymal fat in the fed state. In contrast, LPL activity, mass, and mRNA levels in heart were increased by nicotine whether animals were fed or fasted. These studies provide evidence for multiple mechanistic events underlying nicotine-induced alterations in weight and suggest that nicotine diverts fat storage away from adipose tissue and toward utilization by muscle.

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Regulation of gene expression during meiosis in Saccharomyces cerevisiae: SPR3 is controlled by both ABFI and a new sporulation control element.

Molecular and Cellular Biology ◽

10.1128/mcb.17.3.1152 ◽

1997 ◽

Vol 17 (3) ◽

pp. 1152-1159 ◽

Cited By ~ 37

Author(s):

N Ozsarac ◽

M J Straffon ◽

H E Dalton ◽

I W Dawes

Keyword(s):

Saccharomyces Cerevisiae ◽

Developmental Regulation ◽

Regulation Of Gene Expression ◽

Control Element ◽

Spore Coat ◽

Heterologous Promoter ◽

Specific Manner ◽

Low Levels ◽

Specific Regulation ◽

The Right

The SPR3 gene encodes a sporulation-specific homolog of the yeast Cdc3/10/11/12 family of bud neck filament proteins. It is expressed specifically during meiosis and sporulation in Saccharomyces cerevisiae. Analysis of the sporulation-specific regulation of SPR3 has shown that it is strongly activated under sporulating conditions but shows low levels of expression under nonsporulating conditions. A palindromic sequence located near the TATA box is essential to the developmental regulation of this gene and is the only element directly activating SPR3 at the right time during sporulation. Within the palindrome is a 9-bp sequence, gNCRCAAA(A/T) (midsporulation element [MSE]), found in the known control regions of three other sporulation genes. A previously identified ABFI element is also needed for activation. The MSE has been shown to activate a heterologous promoter (CYC1) in a sporulation-specific manner. Related sequences, including an association of MSE and ABFI elements, have been found upstream of other genes activated during the middle stage of S. cerevisiae sporulation. One group of these may be involved in spore coat formation or maturation.

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Regulation of CRH and AVP mRNA in the developing ovine hypothalamus: effects of stress and glucocorticoids

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.6.e1096 ◽

1995 ◽

Vol 268 (6) ◽

pp. E1096-E1107 ◽

Cited By ~ 20

Author(s):

S. G. Matthews ◽

J. R. Challis

Keyword(s):

Supraoptic Nucleus ◽

Adrenocorticotropic Hormone ◽

Full Term ◽

Late Gestation ◽

Developmental Changes ◽

Mrna Levels ◽

Developmental Profile ◽

Active Labor ◽

Low Levels

Developmental changes in the abundance, localization, and distribution of corticotropin-releasing hormone (CRH) mRNA and arginine vasopressin (AVP) mRNA in the ovine hypothalamus were examined by in situ hybridization. The effects of fetal hypoxemia in the presence or absence of concomitant cortisol in late gestation (day 135) were also investigated. CRH and AVP mRNA were present at low levels within the paraventricular nucleus (PVN) and AVP mRNA was present in the supraoptic nucleus (SON) by day 60 (full term = 147 days). During late gestation, there were increases (P < 0.05, days 140–143 vs. days 100–120) in CRH mRNA, a further increase (P < 0.05, full term vs. days 140–143) at full term (fetuses delivered in active labor), and a subsequent decline postpartum (compared with full term). AVP mRNA in the magnocellular PVN increased (P < 0.05) in late gestation, levels did not change in parvocellular fields compared with full term fetuses, but magnocellular and parvocellular AVP mRNA increased in the newborn (P < 0.05, newborn vs. full term). AVP mRNA in the SON showed a developmental profile similar to that of the PVN, although there was an increase earlier in gestation (P < 0.05, days 100–120 vs. days 60–80). Hypoxemia caused increases (P < 0.05) in CRH mRNA, plasma adrenocorticotropic hormone, and cortisol concentrations, and although magnocellular and parvocellular AVP mRNA appeared elevated, changes just failed to attain significance. Cortisol infusion attenuated the hypoxemia-induced increase in CRH mRNA and adrenocorticotropic hormone but was without effect on basal CRH mRNA levels.

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Temperature-dependent expression of cytochrome-c oxidase in Antarctic and temperate fish

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.277.2.r508 ◽

1999 ◽

Vol 277 (2) ◽

pp. R508-R516 ◽

Cited By ~ 20

Author(s):

I. Hardewig ◽

P. L. M. van Dijk ◽

C. D. Moyes ◽

H. O. Pörtner

Keyword(s):

Enzyme Activity ◽

Cytochrome C ◽

Cold Acclimation ◽

Cytochrome C Oxidase ◽

North Sea ◽

Low Temperatures ◽

Mrna Levels ◽

The North ◽

The North Sea ◽

Low Levels

Seasonal acclimation versus permanent adaptation to low temperatures leads to a differential response in the expression of cytochrome- c oxidase (CCO) in temperate and Antarctic eelpouts. Although eurythermal eelpout from the North Sea ( Zoarces viviparus) displayed a cold-induced rise of CCO activity in white muscle, enzyme activity in the cold stenothermal Antarctic eelpout Pachycara brachycephalum failed to reflect such a compensatory increase. In Antarctic eelpout, CCO activity correlates with transcript levels of mitochondrial encoded subunits of CCO (CCO I and CCO II), whereas cold-acclimated eelpout from the North Sea show lower enzyme activities than expected on the basis of mitochondrial mRNA levels. In these animals, CCO expression at low temperatures may be limited either by nuclear CCO transcripts or by posttranscriptional processes. These may comprise translation of the subunits or assembly of the CCO holoenzyme. mRNA levels of CCO IV, one of the nuclear encoded subunits, increased strongly during cold acclimation, indicating that the expression of CCO is likely not message limited in cold-acclimated Z. viviparus. Our data suggest that seasonal cold acclimation of Z. viviparus results in a modification of the relationship between transcription and translation or posttranslational processes. In permanently cold-adapted P. brachycephalum, on the other hand, CCO expression shows similar characteristics as in the warm-acclimated confamilial species, e.g., low levels of enzyme activity correlated with low levels of mitochondrial message.

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Developmental expression of human angiotensinogen in transgenic mice

AJP Renal Physiology ◽

10.1152/ajprenal.1998.274.5.f932 ◽

1998 ◽

Vol 274 (5) ◽

pp. F932-F939 ◽

Cited By ~ 2

Author(s):

Gongyu Yang ◽

Curt D. Sigmund

Keyword(s):

In Situ Hybridization ◽

Transgenic Mice ◽

Developmental Regulation ◽

Rnase Protection Assay ◽

Late Gestation ◽

Developmental Expression ◽

Rnase Protection ◽

Adult Mice ◽

Specific Regulation

Transgenic mice containing the human angiotensinogen ( HAGT) gene were utilized to determine the developmental regulation of HAGT expression. RNase protection assay on total RNA obtained from whole transgenic fetuses revealed that HAGT expression was first detected at embryonic day 8.5( E8.5) and was abundant from E9.5 onward. The earliest expression of the HAGT transgene appeared to precede the earliest expression of the endogenous mouse AGT gene by 1–2 days. Northern blot analysis revealed moderate levels of HAGT mRNA in liver and kidney and low levels of HAGT mRNA in heart and brain from E16.5 ( day 16.5 of gestation) onward. HAGT mRNA in liver, although abundant during late gestation and in 2-wk-old and adult mice, decreased transiently around birth. In situ hybridization performed on sections from whole fetuses revealed that HAGTmRNA was restricted to the developing liver and heart between E9.5 and E11.5 but became more widespread to include the developing aorta, brain, subcutaneous tissues, and vertebra at E13.5. In situ hybridization analysis on fetal kidneys from late gestation, newborn, and 2-wk-old mice demonstrated a progressive restriction of HAGT mRNA to developing cortical proximal tubular cells. These data illustrate the developmental tissue-specific regulation of HAGTexpression and demonstrate that sequences present in the transgene can confer an appropriate developmental expression profile.

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Hepatocellular expression of glucose-6-phosphatase is unaltered during hepatic regeneration

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.275.4.g717 ◽

1998 ◽

Vol 275 (4) ◽

pp. G717-G722 ◽

Cited By ~ 3

Author(s):

Wisam F. Zakko ◽

Carl L. Berg ◽

John L. Gollan ◽

Richard M. Green

Keyword(s):

Gene Expression ◽

Enzyme Activity ◽

Protein Expression ◽

Partial Hepatectomy ◽

Initial Phase ◽

Physiological Function ◽

Liver Homogenate ◽

Hepatic Regeneration ◽

Mrna Levels ◽

Microsomal Enzyme

Gluconeogenesis and glycogenolysis are essential hepatic functions required for glucose homeostasis. During the initial phase of hepatic regeneration, the immediate-early genes (IEG) are rapidly expressed, and the IEG RL-1 encodes for glucose-6-phosphatase (G-6- Pase). G-6- Pase is a microsomal enzyme essential for gluconeogenesis and glycogenolysis. This study employs a partial-hepatectomy model to examine the expression and activity of G-6- Pase. After partial hepatectomy, rat hepatic G-6- Pase gene expression is transcriptionally regulated, and mRNA levels are increased ≈30-fold. However, in contrast to this rapid gene induction, microsomal enzyme activity is unchanged after partial hepatectomy. Western blotting demonstrates that microsomal G-6- Pase protein expression is also unchanged after partial hepatectomy, and similar results are also noted in whole liver homogenate. Thus, despite marked induction in gene expression of the IEG G-6- Pase after partial hepatectomy, protein expression and enzyme activity remain unchanged. These data indicate that, although this hepatocyte IEG is transcriptionally regulated, the physiologically important level of regulation is posttranscriptional. This highlights the importance of correlating gene expression of IEG with protein expression and physiological function.

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Genomic structure of murine methylmalonyl-CoA mutase: evidence for genetic and epigenetic mechanisms determining enzyme activity

Biochemical Journal ◽

10.1042/bj2960663 ◽

1993 ◽

Vol 296 (3) ◽

pp. 663-670 ◽

Cited By ~ 13

Author(s):

M F Wilkemeyer ◽

E R Andrews ◽

F D Ledley

Keyword(s):

Enzyme Activity ◽

Steady State ◽

Transcription Initiation ◽

Cultured Cells ◽

Genomic Structure ◽

Genetic Regulation ◽

Regulatory Elements ◽

Transcription Unit ◽

Mrna Levels ◽

Sequence Motifs

Methylmalonyl-CoA mutase (MCM) is a nuclear-encoded mitochondrial matrix enzyme. We have reported characterization of murine MCM and cloning of a murine MCM cDNA and now describe the murine Mut locus, its promoter and evidence for tissue-specific variation in MCM mRNA, enzyme and holo-enzyme levels. The Mut locus spans 30 kb and contains 13 exons constituting a unique transcription unit. A B1 repeat element was found in the 3′ untranslated region (exon 13). The transcription initiation site was identified and upstream sequences were shown to direct expression of a reporter gene in cultured cells. The promoter contains sequence motifs characteristic of: (1) TATA-less housekeeping promoters; (2) enhancer elements purportedly involved in co-ordinating expression of nuclear-encoded mitochondrial proteins; and (3) regulatory elements including CCAAT boxes, cyclic AMP-response elements and potential AP-2-binding sites. Northern blots demonstrate a greater than 10-fold variation in steady-state mRNA levels, which correlate with tissue levels of enzyme activity. However, the ratio of holoenzyme to total enzyme varies among different tissues, and there is no correlation between steady-state mRNA levels and holoenzyme activity. These results suggest that, although there may be regulation of MCM activity at the level of mRNA, the significance of genetic regulation is unclear owning to the presence of epigenetic regulation of holoenzyme formation.

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