| 1. |
- Skoog, Maria, et al.
(författare)
-
ACTH reduces the rise in ApoB-48 levels after fat intake.
- 2007
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 191:2, s. 433-439
-
Tidskriftsartikel (refereegranskat)abstract
- It has been repeatedly demonstrated that ACTH administration lowers plasma lipid concentrations in man. The present study was designed to test the hypothesis, based on observations of decreased apolipoprotein B (ApoB) synthesis and secretion in vitro, that ACTH administration inhibits the postprandial output of ApoB in man. Therefore, we studied the response to a fat-rich meal supplemented with Vitamin A in eight healthy volunteers, who underwent this test without premedication, after 4 days administration of ACTH, and after 4 days administration of a glucocorticoid (betamethasone). As expected, fasting plasma levels of low-density lipoproteins (LDL)-cholesterol (−25%) and ApoB (−17%) decreased after ACTH, but not after betamethasone administration. Also, the elevation of plasma ApoB-48 in response to fat intake (to twice the basal levels) was markedly reduced after ACTH administration. However, the postprandial rise in plasma triglycerides and retinyl palmitate was unimpaired, suggesting that ACTH administration induced the secretion of fewer but larger chylomicrons. The effect of betamethasone on the postprandial response was similar but less pronounced. This study confirms earlier reports on the lipid-lowering effects of ACTH and supports our theory, based on in vitro studies, that the lipid-lowering effects of ACTH administration in man involves an inhibition of ApoB production.
|
|
| 2. |
- Skoog, Maria, et al.
(författare)
-
Lipid synthesis and secretion in HepG2 cells is not affected by ACTH
- 2010
-
Ingår i: Lipids in Health and Disease. - 1476-511X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein B (apoB) containing lipoproteins, i.e. VLDL, LDL and Lp(a), are consequently lowered by ACTH treatment in humans. This is also seen as reduced plasma apoB by 20-30% and total cholesterol by 30-40%, mostly accounted for by a decrease in LDL-cholesterol. Studies in hepatic cell line (HepG2) cells showed that apoB mRNA expression is reduced in response to ACTH incubation and is followed by a reduced apoB secretion, which may hypothesize that ACTH lowering apoB containing lipoproteins in humans may be mediated by the inhibition of hepatic apoB synthesis. This was recently confirmed in vivo in a human postprandial study, where ACTH reduced transient apoB48 elevation from the small intestine, however, the exogenic lipid turnover seemed unimpaired. In the present study we investigated if lipid synthesis and/or secretion in HepG2 cells were also affected by pharmacological levels of ACTH to accompany the reduced apoB output. HepG2 cells were incubated with radiolabelled precursors ([C-14] acetate and [H-3] glycerol) either before or during ACTH stimuli. Cellular and secreted lipids were extracted with chloroform: methanol and separated by the thin layer chromatography (TLC), and [C-14] labelled cholesterol and cholesteryl ester and [H-3] labelled triglycerides and phospholipids were quantitated by the liquid scintillation counting. It demonstrated that ACTH administration did not result in any significant change in neither synthesis nor secretion of the studied lipids, this regardless of presence or absence of oleic acid, which is known to stabilize apoB and enhance apoB production. The present study suggests that ACTH lowers plasma lipids in humans mainly mediated by the inhibition of apoB synthesis and did not via the reduced lipid synthesis.
|
|
| 3. |
- Berggren Söderlund, Maria, et al.
(författare)
-
Biological variation of retinoids in man.
- 2002
-
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 62:7, s. 511-519
-
Tidskriftsartikel (refereegranskat)abstract
- This investigation was undertaken to assess biological variation, especially the within-subject variations of all- trans retinoic acid, 13- cis retinoic acid and retinol in human serum. Diurnal variation and variation over a week, a month and a year were studied in 11 males (aged 21 - 54 years) and 17 females (aged 22 - 63 years), all subjectively healthy. We found no diurnal variation with the exception of all- trans retinoic acid, which had maximal concentrations at noon irrespective of food intake. Seasonal variations were marginal. Both all- trans and 13- cis retinoic acids had fairly high within-subject (13.1% and 12.6%, respectively) and between-subject coefficients of variation (15.9% and 21.0%, respectively), while the within-subject CV of retinol was less (5.6%, with a between-subject CV of 21.1%). Thus, the indices of individuality were <1 for all retinoids. The critical differences between two consecutive samples were <40% for the retinoic acids and <20% for retinol. Women had higher all- trans retinoic acid concentrations in serum (5.1 nmol/L vs. 4.5 nmol/L), lower 13- cis retinoic acid concentrations (4.5 nmol/L vs. 5.5 nmol/L) and lower retinol concentrations in serum (2.1 µmol/L vs. 2.5 µmol/L) than men. Thus, samples for retinoid determinations should be drawn in the morning and evaluated using separate gender reference intervals.
|
|
| 4. |
- Berggren Söderlund, Maria, et al.
(författare)
-
Concentrations of retinoids in early pregnancy and in newborns and their mothers.
- 2005
-
Ingår i: American Journal of Clinical Nutrition. - 1938-3207. ; 81:3, s. 633-636
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Retinoids are vital for embryonic development; both excesses and deficiencies of vitamin A are known to give similar patterns of birth defects. Concentrations of retinol in newborns and in pregnant women have been investigated, but concentrations of the biologically active metabolite all-trans retinoic acid and its isomer 13-cis retinoic acid have not. Objective: We measured serum concentrations of these retinoid derivatives in newborns and their mothers and in women in the first trimester of pregnancy, when embryonic differentiation (organogenesis) takes place. Design: In this descriptive study, 10 newborns from normal deliveries and their mothers and 16 healthy women in their first trimester of pregnancy were studied. Seventeen healthy women served as control subjects. all-trans and 13-cis Retinoic acid and retinol concentrations were measured by HPLC. Results: The newborns had significantly lower retinol concentrations (1.0 mu mol/L) than did their mothers (1.7 mu mol/L; P = 0.013). Serum all-trans retinoic acid was also significantly lower in the newborns (3.4 nmol/L) than in their mothers (5.8 nmol/L; P = 0.008). In addition, serum concentrations of 13-cis retinoic acid were significantly lower in the newborns (2.0 nmol/L) than in their mothers (2.6 nmol/L; P = 0.005). The serum concentrations of all-trans retinoic acid and retinol did not correlate in any group. Conclusion: Retinol concentrations do not accurately reflect the concentrations of the biologically active derivative all-trans retinoic acid.
|
|
| 5. |
|
|
| 6. |
- Berggren Söderlund, Maria, et al.
(författare)
-
Expression of human all-trans-retinoic acid receptor beta and its ligand-binding domain in Escherichia coli
- 1995
-
Ingår i: Biochemical Journal. - 0264-6021. ; 308:Pt 1, s. 353-359
-
Tidskriftsartikel (refereegranskat)abstract
- all-trans-Retinoic acid, one of the hormonally active derivatives of vitamin A, occurs physiologically in plasma at a concentration below 10 nmol/l. The methods currently used for its quantification are based on HPLC, need about 1 ml of serum, are relatively laborious and thus not well suited for mass analysis. The affinity and specificity of retinoic acid receptors for all-trans-retinoic acid encouraged us to express both the entire human retinoic acid receptor beta (RAR-beta) and two versions of its retinoic acid-binding domain in Escherichia coli in the hope that these recombinant proteins might be used as binders in a ligand-binding assay for all-trans-retinoic acid. The recombinant receptors, the whole receptor [RAR-beta-(V7-Q448)], corresponding to domains A-F, and the ligand-binding domain [RAR-beta-(E149-Q448)], corresponding to domains D-F, were expressed in the vector pET 3d/BL21 (DE3) as inclusion bodies, solubilized with guanidinium chloride, renatured and purified by ion-exchange chromatography. RAR-beta-(P193-Q448), corresponding to domains E-F, was expressed in the vector pET 3d/BL21(DE3)pLysS, and purified by reversed-phase chromatography. Under non-denaturing conditions, the expressed whole receptor [RAR-beta-(V7-Q448)] and the D-F construct (RAR-beta-(E149-Q448)] behaved chromatographically as monomeric proteins whereas the E-F construct [RAR-beta-(P193-Q448)] had a strong tendency to aggregate. RAR-beta-(V7-Q448) and RAR-beta-(E149-Q448) had similar Kd values for all-trans-retinoic acid (1.4 and 0.6 nmol/l respectively) whereas RAR-beta-(P193-Q448) bound all-trans-retinoic acid less avidly (Kd 9.6 nmol/l). 9-cis-Retinoic acid bound to RAR-beta-(E149-Q448) and RAR-beta-(V7-Q448) as avidly as all-trans-retinoic acid. Competition experiments showed weak or no binding of 4-oxo-all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid, 13-cis-retinoic acid, acitretin and retinol by RAR-beta-(E149-Q448).
|
|
| 7. |
- Berggren Söderlund, Maria
(författare)
-
The informational value and usefulness of serum retinoid measurements. Studies on biological variation, including infancy and pregnancy, and influence of fasting, antiepileptic drugs and ethanol
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of these studies were to evaluate retinoid measurements, more specifically the performance of all-trans and 13-cis retinoic acids methods in clinical experimental settings and to evaluate the informational value of these measurements in relation to S-Retinol. Biological and analytical variations for retinoids were evaluated for healthy subjects. The performance of the retinoic acid measurements generally satisfied clinical demands to identify deficiency and toxicity, and to monitor substitution treatment. However, due to the comparatively large biological variation, it is important to stratify populations in order to obtain separate reference intervals for sub-populations. Also, to identify minor deviations in the set-point of individual subjects, repeated sampling is recommended. For characterisation of vitamin A status, S-All-trans retinoic acid was found to give differential or additional information compared to S-Retinol (which is the most commonly used analysis in this context) in a number of situations. These were: - diurnal variations in S-All-trans retinoic acid but not in S-Retinol - alterations in retinoid metabolism in pregnancy (increasing S-All-trans retinoic acid while S-Retinol remains constant) - low retinoid concentrations in infants (placental cords) - lowered S-All-trans retinoic acid but not S-Retinol during antiepileptic medication. Although S-All-trans retinoic acid and S-Retinol both decreased during caloric restriction, it was evident that individual changes in S-Retinol were poor predictors of individual changes in S-All-trans retinoic acid. Our studies demonstrated that all-trans retinoic acid and 13-cis retinoic acid measurements gave additional information compared to retinol measurements. Determination of retinoic acids is useful and essential in studies on specific issues in vitamin A metabolism. S-All-trans retinoic acid is a promising analyte with considerable potential in a number of clinical situations, especially in vitamin A deficiency. More studies on the informational value of S-13-cis retinoic acid in relation to teratogenicity and toxicity are required.
|
|
| 8. |
- Berggren Söderlund, Maria, et al.
(författare)
-
Vitaminer och spårämnen
- 2018. - 10
-
Ingår i: Laurells Klinisk kemi i praktisk medicin. - Lund : Studentlitteratur AB. - 9789144119748 ; , s. 681-703
-
Bokkapitel (refereegranskat)
|
|
| 9. |
- Di, Dongmei, et al.
(författare)
-
ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells
- 2012
-
Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 421:1, s. 152-156
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously reported that liver X receptor (LXR) agonist, TO901317, could significantly inhibit hepatic apolipoprotein M (apoM) expression. It has been reported that TO901317 could activate the ATP-binding cassette transporter A1 (ABCA1) that mediates cholesterol efflux to the lipid-poor apoA1, which is an essential step for the high-density lipoprotein (HDL) formation. It is unknown if ABCA1 may regulate hepatic apoM expression. In the present study, HepG2 cells were cultured with the synthetic LXR agonists, TO901317 or GW3965 in the presence or absence of ABCA1 antagonist, disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS). The mRNA levels of ABCA1, apoM and liver receptor homolog-1 (LRH-1) determined by the real-time RT-PCR. It demonstrated that both TO901317 and GW3965 could significantly enhance ABCA1 expression, and simultaneously, inhibit LRH1 expression. However, TO901317 alone could significantly inhibit apoM expression, while GW3965 alone did not influence apoM expression. ABCA1 antagonist, DIDS, have no effects on GW3965 induced upregulation of ABCA1 and downregulation of LRH1. However, apoM mRNA level was significantly decreased when the cells cultured with GW3965 together with DIDS. The present study demonstrated that apoM expression could be elevated by ABCA1 via the RXR/LXR pathway and LRH1 does not involve in the regulation of apoM by the activation of ABCA1, although the direct regulative pathway(s) between ABCA1 and apoM gene is still unknown yet. The detailed mechanism needs further investigation. (C) 2012 Elsevier Inc. All rights reserved.
|
|
| 10. |
- Fex, G, et al.
(författare)
-
Low serum concentration of all-trans and 13-cis retinoic acids in patients treated with phenytoin, carbamazepine and valproate. Possible relation to teratogenicity
- 1995
-
Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 69:8, s. 572-574
-
Tidskriftsartikel (refereegranskat)abstract
- All-trans retinoic acid deficiency resulting from ethanol's interference with the synthesis of all-trans retinoic acid from retinol was recently suggested to cause the malformations of the fetal alcohol syndrome. Phenytoin, carbamazepine and valproate, might be teratogenic because they lower the concentration of all-trans retinoic acid in serum, by inducing the enzyme systems in the liver responsible for the metabolism of the all-trans retinoic acid, or by other mechanisms. Here we show, that in patients given therapeutic doses of phenytoin, carbamazepine and valproate, serum all-trans and 13-cis retinoic acid concentrations are indeed significantly lowered. We propose that drugs with this ability should be considered as potential teratogens.
|
|
