scholarly journals Developmental changes in carnitine palmitoyltransferases I and II gene expression in intestine and liver of suckling rats

1995 ◽  
Vol 306 (2) ◽  
pp. 379-384 ◽  
Author(s):  
G Asins ◽  
D Serra ◽  
G Arias ◽  
F G Hegardt

Carnitine palmitoyltransferase (CPT) I is expressed in the intestine of suckling rats; its mRNA increases very rapidly after birth, remains on a plateau until day 18 and decreases until weaning, when basal (adult) values are reached, which remain unchanged thereafter. CPT II mRNA values do not show any appreciable change in this period. CPT I and CPT II are expressed mainly in mucosa and, to a lesser extent, in the muscular part of the intestine. Intestinal expression of CPT I is maximal in duodenum and jejunum, whereas CPT II is expressed in a similar pattern throughout the whole intestine. Dam's milk may influence the intestinal expression of CPT I, since mRNA levels at birth are low but increase after the first lactation. Moreover, rats weaned at either day 18 or 21 decrease their mRNA levels. Apparently, CPT II gene expression is not influenced by the mother's milk. CPT I and CPT II are also expressed in the liver of suckling rats. Hepatic CPT I is maximal at day 3, and levels of CPT II mRNA do not change, in a similar fashion to that in intestine. The profile of expression of CPT I in liver and intestine strongly resembles that previously reported for mitochondrial 3-hydroxy-3-methyl-glutaryl-CoA synthase.

1993 ◽  
Vol 292 (2) ◽  
pp. 493-496 ◽  
Author(s):  
S Thumelin ◽  
M Forestier ◽  
J Girard ◽  
J P Pegorier

The tissue-specific expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene was studied in 15-day-old suckling rats. The mRNA and protein were present in liver, intestine and kidney, but were absent from brain, heart, skeletal muscles, brown and white adipose tissues. Kidney-cortex mitochondria from suckling rats were able to produce low amounts of ketone bodies from oleate. Hepatic, intestinal and renal HMG-CoA synthase mRNA levels increased slowly during foetal life and markedly after birth. The postnatal increase in liver HMG-CoA synthase mRNA could be due to the increase in plasma glucagon levels, since it rapidly induced the accumulation of HMG-CoA synthase mRNA in cultured foetal hepatocytes. Hepatic, intestinal and renal HMG-CoA synthase mRNA levels remained elevated throughout the suckling period or in rats weaned on to a high-fat carbohydrate-free diet (HF), but decreased by 50% in the liver and totally disappeared from the intestine and the kidney of rats weaned on to a high-carbohydrate low-fat diet (HC). When HC-weaned rats were fed on a HF-diet for a week, HMG-CoA synthase mRNA was re-induced in the intestine and the kidney. The role of hormones and nutrients in the regulation of HMG-CoA synthase gene expression is discussed.


1994 ◽  
Vol 299 (1) ◽  
pp. 65-69 ◽  
Author(s):  
G Asins ◽  
J L Rosa ◽  
D Serra ◽  
G Gil-Gómez ◽  
J Ayté ◽  
...  

Levels of mRNA for mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase, carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II), fatty acid synthase (FAS) and actin were analysed during liver regeneration. mRNA levels for mitochondrial HMG-CoA synthase decreased rapidly, reaching a minimum 12 h after partial hepatectomy and returning to normal at 24-36 h. In contrast, CPT I, CPT II and FAS mRNAs increased throughout the period examined. Expression of actin increased significantly during regeneration. Levels of mRNA for mitochondrial HMG-CoA synthase also decreased as a result of surgical stress, although the effect of hepatectomy was much greater. We determined the levels of mitochondrial HMG-CoA synthase using specific antibodies. The amount of protein rapidly decreased, although less markedly than the corresponding mRNA levels. These results show that the decrease described in ketogenesis in partially hepatectomized rats correlated with the decrease in the expression of mitochondrial HMG-CoA synthase, suggesting that this enzyme may also be a control point in ketogenesis in the regenerating liver, as it is in normal and diabetic rats.


2000 ◽  
Vol 78 (5) ◽  
pp. 400-406 ◽  
Author(s):  
Jaques Belik ◽  
Brad Karpinka ◽  
David A Hart

During development, the vascular wall composition of the pulmonary and systemic capacitance vessels and their intravascular pressure changes. Little is known, however, about the factors controlling vascular collagen gene expression in both circulations during growth and development. The purpose of this study was to compare the developmental changes in collagen, major growth factors, and cytokines gene expression, in order to ascertain whether a circulation specific pattern is present in the rabbit. Fetal, neonatal, and adult rabbit extrapulmonary and aortic tissues were obtained and the mRNA levels for collagen I and III, as well as major growth factors and cytokines, were measured by a semi-quantitative RT-PCR technique. Collagen I, but not collagen III, expression was developmentally regulated in pulmonary vascular and aorta tissues. Collagen I expression was greatest during the fetal and neonatal period (P < 0.01) and higher in the aorta as compared with the pulmonary artery at these ages (P < 0.05). Significant developmental changes in growth factor mRNA levels were observed for TGF-beta, IGF-2, and bFGF (P < 0.01). IGF-2 mRNA levels significantly declined in both arteries from neonatal to adult, but bFGF increased only in the pulmonary artery during this transition. With regards to inducible enzymes, COX-2 mRNA levels changed developmentally, whereas iNOS mRNA levels were similar for both vessels at all ages. When comparing the two vessels, COX-2 transcripts were relatively more abundant in the adult pulmonary artery tissue and fetal aorta, with similar levels in the newborn. We conclude that circulation specific developmental regulation of collagen gene expression is present in the rabbit in a pattern that is unrelated to the intravascular pressure. Key words: developmental changes, vascular, collagen, mRNA expression, growth factors.


2001 ◽  
Vol 280 (2) ◽  
pp. E270-E279 ◽  
Author(s):  
Anne Minnich ◽  
Nian Tian ◽  
Lisa Byan ◽  
Glenda Bilder

The proposed mechanism for the triglyceride (TG) lowering by fibrate drugs is via activation of the peroxisome proliferator-activated receptor-α (PPARα). Here we show that a PPARα agonist, ureido-fibrate-5 (UF-5), ∼200-fold more potent than fenofibric acid, exerts TG-lowering effects (37%) in fat-fed hamsters after 3 days at 30 mg/kg. In addition to lowering hepatic apolipoprotein C-III (apoC-III) gene expression by ∼60%, UF-5 induces hepatic mitochondrial carnitine palmitoyltransferase I (CPT I) expression. A 3-wk rising-dose treatment results in a greater TG-lowering effect (70%) at 15 mg/kg and a 2.3-fold elevation of muscle CPT I mRNA levels, as well as effects on hepatic gene expression. UF-5 also stimulated mitochondrial [3H]palmitate β-oxidation in vitro in human hepatic and skeletal muscle cells 2.7- and 1.6-fold, respectively, in a dose-related manner. These results suggest that, in addition to previously described effects of fibrates on apoC-III expression and on peroxisomal fatty acid (FA) β-oxidation, PPARα agonists stimulate mitochondrial FA β-oxidation in vivo in both liver and muscle. These observations suggest an important mechanism for the biological effects of PPARα agonists.


1996 ◽  
Vol 329 (1) ◽  
pp. 82-86 ◽  
Author(s):  
Guillermina Asins ◽  
Dolors Serra ◽  
Angel Miliar ◽  
Concepción Caudevilla ◽  
Raquel Matas ◽  
...  

1999 ◽  
Vol 340 (2) ◽  
pp. 425-432 ◽  
Author(s):  
Michelle L. STEFFEN ◽  
Wilbur R. HARRISON ◽  
Frederick F. B. ELDER ◽  
George A. COOK ◽  
Edwards A. PARK

Carnitine palmitoyltransferase (CPT)-I catalyses the transfer of long-chain fatty acids from CoA to carnitine for translocation across the mitochondrial inner membrane. Expression of the ‘liver’ isoform of the CPT-I gene (CPT-Iα) is subject to developmental, hormonal and tissue-specific regulation. To understand the basis for control of CPT-Iα gene expression, we have characterized the proximal promoter of the CPT-Iα gene. Here, we report the sequence of 6839 base pairs of the promoter and the localization of the rat CPT-Iα gene to region q43 on chromosome 1. Our studies show that the first 200 base pairs of the promoter are sufficient to drive transcription of the CPT-Iα gene. Within this region are two sites that bind both Sp1 and Sp3 transcription factors. In addition, nuclear factor Y (NF-Y) binds the proximal promoter. Mutation at the Sp1 or NF-Y sites severely decreases transcription from the CPT-Iα promoter. Other protein binding sites were identified within the first 200 base pairs of the promoter by DNase I footprinting, and these elements contribute to CPT-Iα gene expression. Our studies demonstrate that CPT-Iα is a TATA-less gene which utilizes NF-Y and Sp proteins to drive basal expression.


2001 ◽  
Vol 385 (2) ◽  
pp. 283-289 ◽  
Author(s):  
Angel Miliar ◽  
Dolors Serra ◽  
Ricardo Casaroli ◽  
Senén Vilaró ◽  
Guillermina Asins ◽  
...  

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