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Biomedical subjects

M Castrén

Publications and source records attributed to M Castrén.

26 records · Page 2Linked to original sources
PubMed1995

Transcriptional induction of rat mineralocorticoid receptor gene in neurones by corticosteroids.

We investigated the mechanisms by which corticosteroids regulate the expression of the mineralocorticoid receptor (MR) in neurones. Aldosterone and dexamethasone produced a dose-dependent increase of MR and mRNA levels in cultured primary hippocampal neurones. Transient transfection of neuroblastoma cells showed that corticosteroids directly activate the rat MR promoter, indicating that the steroid-induced increase in the MR mRNA concentration is at least partially transcriptional. Progressive 5' deletions of the MR promoter sequence revealed that the promoter induction cannot be assigned to a single element. An oligonucleotide comprising a consensus half-glucocorticoid responsive element located at -319 bp in the MR promoter stimulated the corticosteroid-induced activation of the heterologous promoter. Cloning three of these enhancers in tandem greatly potentiated the responses to glucocorticoids and mineralocorticoids, suggesting that although this element is a weak enhancer it can, in combination with other enhancer elements, induce MR gene expression by both types of corticosteroid receptors.

Adrenal Cortex Hormones↗
PubMed1994

Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS.

In the mammalian central nervous system, responsiveness to glucocorticoids is mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). These pharmacologically distinct receptors are believed to bind to common response elements as homodimers. We provide evidence that MR and GR can form a heterodimeric complex with DNA-binding and transactivation properties different from those of the respective homodimers. There was a high degree of cooperativity of MR and GR in binding to a glucocorticoid response element. Transient transfection of a neuroblastoma cell line revealed a transcriptional response pattern of coexpressed MR and GR distinct from that obtained by MR or GR alone. Our findings demonstrate that heterodimerization of MR and GR is a hitherto unrecognized principle for the transcriptional regulation of glucocorticoid-responsive genes in tissue coexpressing these receptors.

Base Sequence↗
PubMed1993

A functional promoter directing expression of a novel type of rat mineralocorticoid receptor mRNA in brain.

The authors have identified two types of hippocampal cDNAs for the rat mineralocorticoid receptor (rMR) which are identical in the protein coding domain but differ in their 5'-untranslated sequences. One of these clones encodes a novel type of rMR cDNA with a high homology to a previously described human MR cDNA isolated from the kidney. A genomic clone containing the 5'-end of the rat MR gene was isolated. The 12.7 kb genomic region contains the 5'-coding exon with the translational start site and contiguous DNA sequences encoding the N-terminal domain of the rMR. A 240 bp region homologous to the 5'-untranslated sequences of the novel rMR cDNA was located 5.2 kb upstream the protein coding region. Characterization of the nucleotide sequence preceding this exon revealed several features characteristic for promoters of so-called 'housekeeping genes'. The sequence analyzed is 635 bp in length, is rich in G+C nucleotides (63%) and lacks TATA or CAAT regulatory elements. It contains three putative binding sites for transcription factor Sp1 as well as several short sequences that are similar to known cis-acting enhancers or binding sites for transcription factors. In transient transfection experiments employing the luciferase reporter gene and the CV1 cell line this region exhibits substantial promoter activity. These experiments demonstrate that expression of the rat MR gene in the hippocampus results in at least two transcripts with different 5'-untranslated exons.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

X-linked anhidrotic ectodermal dysplasia and de novo t(X;1) in a female.

A de novo translocation (X;1)(q13.1;p36.33) was found in a 2-year-old girl with typical clinical features of X-linked anhidrotic ectodermal dysplasia (EDA). The breakpoint at Xq13.1 is approximately the same as has been described in 2 other EDA females with X;autosome translocations.

Child, Preschool↗
PubMed1987

Changes of the liver UDP-glucuronosyltransferase activity in trout (Salmo gairdneri Rich.) acutely exposed to selected aquatic toxicants.

Rainbow trout were exposed for 4 or 8 days to various types of toxicants, each applied to the test water at a high sublethal concentration. The activity of liver UDP-glucuronosyltransferase (UDP-GT) was assayed from the submitochondrial fraction using p-nitrophenol as an aglycone. Activity of UDP-GT was inhibited by 2,4,6-trichlorophenol, pentachlorophenol and dehydroabietic acid, all toxicants regularly found in effluents of the pulp and paper industry. The heavy metals cadmium and zinc, the polychlorinated biphenyl, Pyralene 3010, and chloroform did not affect UDP-GT activity. The slimicide N-methyl-dithiocarbamate (Vapam) significantly increased the enzyme activity.

Abietanes↗
PubMed1986

Drug- and temperature-induced changes in peripheral circulation measured by laser-Doppler flowmetry and digital-pulse plethysmography.

We measured the effects of a new transdermal nitroglycerin patch (25 mg, 10 cm2) applied for 24 h, norphenephrine (6 mg), prazosin (1 mg) as well as local heat and cold provocation on blood pressure, heart rate, skin blood flow (measured by laser-Doppler flowmetry, L-D) and peripheral arterial resistance (assessed by digital pulse plethysmography, D-P) in 15 healthy volunteers (aged 21-31 years). Heat provocation induced a three-fold increase in skin blood flow in the hand (p less than 0.001) and cold provocation a decrease in flow (p less than 0.05) of about 20%. Forehead skin blood flow did not change. Peripheral arterial resistance showed less consistent changes during the provocation tests. Prazosin increased the forehead skin blood flow (p less than 0.01) and decreased peripheral arterial resistance, while norphenephrine showed an opposite effect. Transdermal nitroglycerin induced an increase of 25% in forehead skin blood flow (p less than 0.05) which persisted for 24 h and a decrease in peripheral arterial resistance (p less than 0.02), but this effect was evident up to 8 h only. We conclude that (1) local heat and cold provocation mainly affected skin blood flow, (2) vasodilative and vasoconstrictive drugs showed marked changes in peripheral arterial resistance, but at different points in time from subject to subject, and (3) transdermal nitroglycerin patches induced haemodynamic changes persisting for up to 8-24 h.

2-Hydroxyphenethylamine↗
PubMed1983

Optimal assay conditions for liver UDP-glucuronosyltransferase from the rainbow trout, Salmo gairdneri.

Several kinetic characteristics and assay dependence of UDP-glucuronosyltransferase were studied with microsomal preparations made from liver of rainbow trout. The optimal enzyme assay, performed by incubating less than 5 mg microsomal protein/ml assay buffer for 20 min at 25 degrees C and in pH 7.0, contains 2.5 X 10(-5) M p-nitrophenol (p-NP) and 2.5 X 10(-3) M UDP-glucuronic acid (UDPGA). Apparent Km values revealed that the affinity of trout enzyme for p-NP and UDPGA is, respectively, about 70 and 10 times higher than that of rat enzyme. The optimized method will be used for aquatic bioassays, e.g. when assessing the influencing of toxic effluents from the pulp and paper industry.

Animals↗